text:
EPR Consumer News
Submit Consumer News
Tag Archives: PArcel2Go
Business, Consumer, Consumer Information, Consumer Services, Internet, Reviews, Services
Parcel2Go Helping Small Businesses to Beat Royal Mail Price Increase
June 6, 2012 EPR Consumer News	Leave a comment
Small firms feeling the squeeze following the Royal Mail's decision to increase the price of first and second class stamps at the end of last month are being offered a helping hand by Bolton-based online parcel delivery firm Parcel2Go.
The company says businesses and individuals can try to beat the Royal Mail price increase by becoming Parcel2Go users and benefitting from the vast range of reliable and cost-effective UK express delivery solutions available through the website.
With just a few clicks of a mouse, customers can order delivery services from some of the world's major courier companies such as FedEx, Parcelforce and Yodel. Changes to the way Royal Mail prices parcels means people will be better off sending any consignment weighing more than 750g through Parcel2Go.
Parcel2Go's marketing director Richard Mercer said: "We understand how much pressure consumers and small businesses are under at the moment, which is why we are urging people to see if they are able to get a better deal on their package deliveries through the Parcel2Go website.
"Our quick quote function makes it simple and extremely fast to get a price for a delivery, but that simple move could result in a sizeable saving. What's more, because we only deal with the world's top courier firms, individuals and businesses always know their consignments are in safe hands."
Convenience matters to everyone, which is why the Collect+ services available through Parcel2Go have become so popular. Customers not able to meet a courier to pick up their package can choose instead to drop it off at one of the 3,000 corner shops and convenience stores in the UK that make up the Collect+ network.
"Convenience, speed, reliability and affordability are what we're about," said Mr Mercer. "We're calling on everyone affected by the recent Royal Mail price hike to see if they could save, and get a better service though Parcel2Go."
Via EPR Network
More Consumer press releases
FedExparcel deliveryPArcel2Gopostage ratesUK express delivery
Provide rapid parcel delivery options and reap the benefits, says Parcel2Go
May 31, 2012 EPR Consumer News	Leave a comment
Businesses should look to offer customers a wide range of rapid delivery options if they want to maximise sales opportunities, according to online parcel delivery specialist Parcel2Go.
The Bolton-based company has advised online retailers of all sizes to ensure that they have a variety of solutions available, including next-day, 48-hour, Saturday morning and overseas delivery options. Customers who receive their goods quickly are more likely to leave a positive review of their experience, and new research has shown just how important positive feedback is to UK businesses.
Parcel2Go marketing director Richard Mercer said research carried out by social commerce firm Reevoo had highlighted how much online shoppers value reviews from other customers, and therefore the importance businesses should place on boosting service levels.
He said: "Managing customer orders quickly and efficiently once they have been submitted is critical to the smooth running of any retail company, and research has shown the value that shoppers place on having access to cheap and fast delivery services. It's common sense that they want to receive their items as soon as possible.
"Companies should capitalise on this and make sure that delivery options from the leading firms that people will recognise and trust, such as Parcelforce and FedEx, are easily accessible through the site at the point of sale. If customers receive their products quickly and in top condition, then of course they're more likely to leave a positive review of their experience."
Reevoo's survey found that 88 per cent of the 1,000 customers it questioned said they either "sometimes" or "always" consulted reviews before heading to the checkout.
As well as offering domestic and international freight delivery options from the UK's top couriers, Parcel2Go also provides customers with a parcel tracking facility, so consignments can be monitored no matter where they are in the world.
international freightparcel trackingPArcel2Goparcelforce
Don't Get Caught Out When Sending Parcels To The Relies Down Under, Says Parcel2Go
Online parcel delivery specialist Parcel2Go has reminded anyone planning on sending parcels to relatives or friends living in Australia that shipping goods with a reliable courier company is essential if they want to ensure their package will arrive in one piece.
Australia and New Zealand have become massively popular as destinations to relocate to with Brits of all ages. A survey conducted by research firm YouGov last month found that Australia was the number one destination for Brits considering a move abroad, with the United States and Canada taking second and third place respectively. More than two-fifths (42 per cent) of the 1,650 UK adults polled said they would "seriously consider" leaving Britain, while 6 per cent of respondents said they were actively making plans to leave the country.
With an increasing number of people looking to stay in contact with friends and relatives outside the UK, Parcel2Go's marketing director Richard Mercer has highlighted the importance of using a reliable courier when shipping abroad, and also checking that parcels are safely and securely wrapped before they're sent off.
He said: "With the UK officially back in recession and what seems like more tough times ahead for people in the UK, it is no surprise that the prospect of a move Down Under seems particularly appealing. We just want to remind people that know someone who has taken the plunge and relocated, to take every care to ensure their overseas packages get to Australia safe and sound.
"Using one of the cheap international delivery services available through Parcel2Go makes sense for anyone looking for speed, reliability and value for money. People must also do everything they can to wrap their packages properly and prepare them for a journey of 10,000 miles or so."
cheap international deliverycitylinkparcel deliveryPArcel2Gopostage rates
Parcel2Go Says Firms Should Make The Most Of Growing Online Spend
May 8, 2012 EPR Consumer News	Leave a comment
With people in the UK spending more money online than ever before, companies need to make sure that they have a suitable digital presence to be able to market their goods and services effectively, according to Britain's largest online parcel delivery service.
Parcel2Go helps online companies of all shapes and sizes to deliver customers' orders to addresses across the UK, and around the world, every day. And according to research carried out by payment services firm WorldPay, the average British consumer now spends a quarter of their disposable income with online retailers.
Parcel2Go has seen the effects that increasing consumer confidence and the ease with which people can now buy online have had on parcel delivery volumes. The company's marketing director Richard Mercer said firms must ensure they have suitable parcel delivery systems set up in order to capitalise on the increase in online spend.
He said: "Having a website that is easy to find and intuitive to use is vital if businesses want to draw in customers in the first place. Having a smooth and simple delivery process for when an order has been placed is then vital if they want to keep those customers.
"It has never been more important to have a fast and efficient domestic and international parcel delivery offer. WorldPay's research is evidence of how much consumers have come to rely on the internet when it comes to purchasing goods and services, and Parcel2Go's experience is that customers now expect to receive their goods quickly and in perfect condition.
"Hiring the services of a professional world courier to handle deliveries is now critical."
Parcel2Go assists businesses in organising deliveries to countries across the world, from Spain to Singapore, with the help of some of the industry's leading courier companies, including City Link, Parcelforce, FedEx and UPS.
FedExparcel deliveryPArcel2Gopostage ratesworld courier
Parcel2Go calls on consumers to support British businesses
One of the leading online parcel delivery firms, Parcel2Go, has called on consumers to help get the country's economy back on track by supporting British businesses.
The Office for National Statistics announced last week that the UK economy had gone back into recession, leading to calls for people to be more patriotic when they are making purchases. Parcel2Go has added its voice to the campaign and encouraged shoppers to do what they can to help support British firms.
Richard Mercer, marketing director at Bolton-based Parcel2Go, said: "It's more important than ever that we buy products made in Britain and support British businesses. The internet has made it simple to purchase products from all over the UK, and if companies use the services of reliable courier firms then items can be with consumers extremely quickly.
"As has been said by other retail industry commentators, UK firms also need to make sure that they are promoting themselves and their products properly and ensuring potential customers know if their goods are made in Britain."
With the London 2012 Olympics and the Queen's Diamond Jubilee celebrations both falling within a short space of time, businesses have been advised to do everything possible to make the most of the patriotic mood sweeping across the UK.
Parcel2Go works with a huge variety of British businesses to organise delivery of their products to addresses all over the UK on a daily basis. The company helps individuals and British businesses to deliver more than two million domestic and international parcel consignments every year with the assistance of industry-leading couriers including Parcelforce and City Link.
citylinkinternational parcelparcel deliveryPArcel2Gopostage rates
Retail Results Highlight Importance Of Parcel Delivery Services, Says Parcel2Go
April 24, 2012 EPR Consumer News	Leave a comment
Despite UK retailers feeling the pressure as consumers' incomes continue to be squeezed and shoppers keep a tight rein on their spending, online channels are still delivering impressive results. According to online parcel delivery specialist Parcel2Go, businesses must look to capitalise on the opportunities available and encourage consumers to spend by providing a reliable service and rapid parcel delivery options.
Recent financial results from Marks & Spencer revealed a 22.8 per cent increase in e-commerce sales in the 13 weeks to March 31. That was despite a 0.7 per cent fall in like-for-like sales in the UK. Department store John Lewis also posted impressive online sales results in the week to April 14, with a 57.8 per cent year-on-year increase in sales at johnlewis.com. This followed a 39.1 per cent year-on-year increase the previous week.
According to Richard Mercer, marketing director at Parcel2Go, these latest results highlight just how important online channels have become to retailers, and should serve as a reminder that customers expect goods ordered online to arrive promptly.
He said: "As an increasing number of shoppers become comfortable with shopping over the internet, all businesses must appreciate how vital it is first of all to have an online presence, and then to ensure goods arrive with shoppers quickly and in tip-top condition.
"By calling on the services of reliable and affordable courier firms, all companies can put themselves in the best possible position to win repeat custom."
Results of a survey released earlier this month showed that out of 2,000 online shoppers, 74 per cent had abandoned purchases because they felt the delivery charge was too high, suggesting that the issue postage rates is something else businesses trading on the internet must remain aware of.
Parcel2Go Urges Companies To Take Note Of BRC Online Shopping Statistics
An increasing number of consumers from outside the UK are going online to search for products from British firms that must now react, says Parcel2Go.
Britain's largest online parcel delivery specialist believes businesses have an opportunity to increase the volume of goods they export to customers around the world if only they seize it. Parcel2Go currently helps businesses and individuals in the UK to send more than two million parcels to destinations around the world with courier companiesevery year.
Richard Mercer, marketing director at Parcel2Go, said research from the British Retail Consortium (BRC) and Google had revealed that during the first quarter of 2012, total search volumes from overseas consumers rose by 57 per cent year-on-year.
The BRC/Google search data showed developing countries including Mexico and Pakistan played a significant role in driving traffic to UK sites in the first quarter of the year, with year-on-year growth of 135 per cent and 101 per cent respectively.
Mr Mercer urged companies to take advantage of the fact that more and more foreign shoppers are interested in British brands and products.
He said: "The figures show this is the perfect time for companies here in Britain to capitalise on the interest being shown by foreign consumers in our goods and services. As well as having a strong online presence, businesses must make sure they are clearly offering a range of international parcel delivery options to entice foreign consumers and boost their sales.
"Parcel2Go works with the world's leading parcel delivery companies and it's with the help of cheap international courier businesses that firms here in the UK will be able to prosper in new overseas markets."
cheap international couriercitylinkcourier companiesPArcel2Gopostage rates
Plan Parcel Delivery Needs And Don't Get Caught Out By London 2012, Says Parcel2Go
The UK's largest online parcel delivery specialist has warned individuals and businesses not to get caught out by the inevitable disruption set to be caused by the London 2012 Olympics this summer.
The Olympic Games will take place at sports arenas across the United Kingdom between July 27 and August 12 this year, with the majority of events happening in London. Unsurprisingly, the anticipated influx of visitors to London will have a significant impact on the capital's transport network and may also lead to disruption at Olympic sites across Britain.
Organisers of the Games have already told businesses that road closures and parking restrictions will impact on parcel deliveries and collections. The UK's leading courier companies such as City Link, FedEx and TNT are all working to find ways to minimise the inevitable disruption to customers and are liaising with organisers as part of their attempts to provide reliable services during the Games.
Parcel2Go's marketing director Richard Mercer said: "The London 2012 Olympics will be a huge international event and understandably the sheer volume of people set to descend on the capital and other UK cities will cause disruption and delays. Courier companies are working hard to formulate plans to counter the effect of road closures and parking restrictions, and have pledged to keep customers informed via Olympic delivery information pages.
"Parcel2Go is calling on people to plan ahead as much as possible and make parcel recipients aware of the situation. For now, the best thing is to keep regularly checking couriers' websites for updates on how the Games is likely to affect day-to-day operations."
The parcel tracking services available online through Parcel2Go play a vital role in helping individuals and businesses to remain aware of where their consignments are, and when they are likely to arrive. During the Olympics, these services are expected to be key in assisting customers to stay informed and up-to-date.
FedExparcel deliveryparcel trackingPArcel2Goworld courier
Parcel2Go Backs Government Call For SMEs To Break Into New Overseas Markets
April 6, 2012 EPR Consumer News	Leave a comment
A call by the government's trade and investment minister Lord Green for more small businesses in Britain to attempt to break into new markets overseas has been backed by the UK's largest online parcel delivery service.
Parcel2Go, which assists individuals and businesses in shipping more than two million packages across the globe with world courier firms every year, believes there are significant opportunities waiting for forward-thinking companies.
During a recent appearance in Gateshead, the minister said small businesses sending their products overseas were at the heart of the government's plans to grow the economy. Lord Green said that while the domestic market continued to grow slowly, opportunities were going to come from overseas. He also stressed the importance of looking to new markets outside of the eurozone, such as Asia, the Middle East and the United States.
Parcel2Go's marketing director Richard Mercer said: "Small businesses are certainly central to the economic recovery, and Lord Green is correct in highlighting the importance of overseas markets to businesses in the UK. There are opportunities out there and at Parcel2Go we want to help as many companies as possible beat the downturn and explore avenues for growth further afield.
"It is understandable that small firms especially might be hesitant about attempting to build new customer bases in countries a considerable distance from Britain. However, with the help of partners such as Parcel2Go, which can help take the hassle out of shipping goods abroad, it is possible for these firms to flourish overseas."
Parcel2Go works with some of the world's leading parcel delivery couriers, including Parcelforce, City Link and FedEx, to organise the delivery of parcels to countries across the globe, from Australia to Cyprus. International delivery services to fast-growing economies including Brazil, South Africa and China are also available through the website.
couriers in LondonFedExparcel deliveryPArcel2Goworld courier
Parcel Delivery Firm Backs Findings Of Online Shopping Survey
March 30, 2012 EPR Consumer News	Leave a comment
Bolton-based online parcel delivery specialist Parcel2Go has given its backing to a recent internet shopping survey, which found that high delivery charges had led many consumers to abandon purchases.
A survey of 2,000 UK consumers, carried out by ecommerce specialist Econsultancy, found that nearly three-quarters of people (74 per cent) had abandoned an online purchase because they thought the charge for having their product delivered was too high.
Parcel2Go's marketing director Richard Mercer says this is an issue that all online retailers should be aware of, and work towards addressing.
He said: "The fact that so many consumers have been in the position where they are all ready to go ahead with a purchase, and then have decided to abandon it at the last minute, should certainly start alarm bells ringing with firms. Excessive delivery charges are something that online shoppers are clearly not prepared to put up with.
"Of course the majority of online businesses are not able to go down the same route as the major players such as Amazon and Play.com and offer free parcel delivery as standard, but this survey highlights how important it is to get delivery charges right."
Parcel2Go helps individuals and businesses arrange shipping of more than two million parcels to destinations in the UK and across the world every year. By partnering with some of the leading world couriercompanies such as FedEx, City Link and Parcelforce, Parcel2Go is able to offer its customers access to a huge range of competitively-priced domestic and international delivery services.
Mr Mercer added: "The internet has made it easier than ever for businesses to organise their parcel deliveries, and so by offering low-cost, reliable courier services with parcel tracking through their site, firms can increase the number of shoppers who complete purchases at the checkout."
parcel deliveryparcel trackingPArcel2Goparcelforceworld courier
Don't Miss Out On Opportunities Thrown-Up By The Tablet Explosion, Urges Parcel2Go
The number of people in the UK who own a tablet computer is rising rapidly, and online parcel delivery specialist Parcel2Go has called on companies of all sizes to make sure they don't miss out on the wealth of opportunities available.
The market for tablets has been recognised as one that is significant and growing, with new product releases such as Apple's third generation iPad helping to boost interest in the sector. Apple's first iPad went on sale just over two years ago, and the company has sold around 55 million of the devices since then.
The latest version, which hit the shops earlier this month, had "a record weekend" according to the company and chief executive Tim Cook, who has said he expects tablets to outsell computers within three years.
Parcel2Go's marketing director Richard Mercer said the fact that tablet computer ownership is spreading so rapidly, and that research has shown the average tablet owner spends more money shopping online other internet users, means businesses must act.
He said: "The convenience and ease of browsing and shopping using tablet computers has been recognised by consumers, and businesses must recognise the importance of having a strong online presence in order to take advantage of the situation.
"Parcel2Go helps a large number of companies to get their products out to customers with domestic and international parcel delivery firms. We know that customers have come to demand that businesses today not only offer an online shopping experience that is intuitive and enjoyable, but also one that allows them to have access to delivery services that are fast, reliable, inexpensive and will ensure that the product is in their hands in the shortest possible time."
citylinkinternational parcelparcel deliveryPArcel2GoUK courier
Parcel2Go Highlights The Importance Of Offering A Variety Of Shipping Options On eBay
February 29, 2012 EPR Consumer News	Leave a comment
One of the UK's leading online parcel delivery services has stressed how important it is for UK businesses to make sure they are appealing to as wide a group of online consumers on eBay as possible.
Bolton-based Parcel2Go made the call following an interview given to the Daily Telegraph by the online auction and retail giant's president of global marketplaces this week. Devin Wenig told the newspaper the UK had now become eBay's fastest-growing marketplace, highlighting the fact that the British site receives visits from 17 million unique users every month, with sellers listing 40 million products.
Parcel2Go marketing director Richard Mercer said the news highlights just how important it is for businesses using eBay to ensure that they are doing everything possible to attract customers.
He said: "The popularity of eBay is something that all businesses should be looking to take advantage of. E-commerce is continuing to grow at a staggering pace and companies should be trying to maximise their exposure to potential customers.
"On eBay, one way of doing this is by offering a wide range of shipping options to customers as this will ensure that listings appeal to as wide a range of people as possible. For example, by offering international shipping options through international courier firms you are going to suddenly make your products available to a whole swathe of new customers."
In his interview, Mr Wenig also highlighted the increasing role that mobile is playing, describing its growth as "exponential". He said one item per second is now purchased through a mobile device.
"Smartphone usage is spreading rapidly and as more consumers get access to sites such as eBay while they're on the move, sales will naturally increase. We want as many businesses as possible to benefit from this opportunity," added Richard.
cheap courierFedExinternational shippingPArcel2GoUK mail
Parcel2Go Calls On Businesses To Keep Customers In The Loop During Bad Weather
With more snow expected to hit the UK in the coming days, online parcel delivery specialist Parcel2Go has called on companies to ensure they keep customers expecting deliveries informed.
Forecasters have warned that the cold spell currently gripping Britain could last until the end of the month, with very cold temperatures leading to hard frosts in the coming days. Severe weather warnings for snow and ice are in place across many parts of England and Wales, and Parcel2Go, which helps individuals and businesses to organise more than two million international and UK mail shipments each year, has warned that delays are possible.
In order to help customers stay on top of the latest developments, Parcel2Go has added a new weather warning information link to its homepage which is being updated as necessary with news of the latest weather-related developments affecting postcode areas across the UK.
Parcel2Go's marketing director, Richard Mercer, has called on businesses to check the site for important updates and where necessary, communicate these to customers who are expecting domestic and international parcel deliveries.
He said: "Temperatures have been well below freezing and unsurprisingly this is playing havoc on some of the country's roads.
"Parcel delivery services and collections will continue as normal if it is deemed safe for drivers to reach addresses, but to a large degree we are at the mercy of the elements and as we have seen over the past week, conditions can change extremely quickly.
"We're asking people who are expecting parcels to be collected to bear with us if weather conditions are preventing a driver from calling, and for companies to let their customers know that consignments could be delayed as a result."
courier servicesfed exinternational parcelPArcel2GoUK mail
Parcel2Go hails UK's entrepreneurial spirit
February 6, 2012 EPR Consumer News	Leave a comment
Online parcel delivery specialist Parcel2Go has applauded the drive and will to succeed of the thousands of people across the UK who decide to start their own businesses. In the face of rising unemployment across Britain and the threat of a double-dip recession, entrepreneurs of all kinds are grasping the opportunity to take control of their own future.
Figures released last month by the Office for National Statistics showed the number of people registered as self-employed in the UK increased by 101,000 during the three months to November 2011, representing a 3.5 per cent year-on-year increase.
There are now in excess of 4.12 million self-employed people in the UK – the highest number since comparable records began in 1992. Richard Mercer, marketing director at Parcel2Go, said: "The figures really speak for themselves. They reveal the true entrepreneurial spirit of people in Britain and prove that even in tough economic times, there are individuals out there that are willing to take a chance and put in the hard work, in the hope of reaping rewards in the future.
"Parcel2Go works with a large number of small businesses, including many one-man bands selling products through online retail sites such as eBay. We know how much effort it takes to create a successful business and we want to take the opportunity to applaud those people who have seized the opportunity."
According to recent surveys, it's certainly not just young people in Britain who are finding the 'get up and go' to start their own businesses. An increasing number of 'silver entrepreneurs' are coming to the fore – enterprising pensioners who are looking to use their skills and experience to help boost their pension funds by working as freelance consultants and setting up their own online firms.
Richard added: "We'd urge any new business owner to take a look at the domestic and international parcel delivery service options available on the Parcel2Go website, or browse the Parcel2GO.com Facebook page and discover how we can help their company to grow."
parcel delivery servicePArcel2GoParcel2GO.com Facebooksending parcels abroadUK courier service
Scottish Broadband Plan Would Be Boon To Small Businesses, Says Parcel2Go
New plans to dramatically increase the speed of broadband internet services to homes and businesses in Scotland by 2015 have been welcomed by the UK's largest online parcel delivery specialist.
Parcel2Go, which helps individuals and businesses across Britain to send consignments to addresses here in the UK and countries all over the world, said if the Scottish government's plans come to fruition, the result would be a major boost for small firms.
As part of the Infrastructure Action Plan (IAP), the government hopes that 85 to 90 per cent of properties in Scotland will benefit from broadband speeds of between 40-80Mbps. At the moment the average broadband speed in the UK is just 6.8Mbps.
The growing importance of being able to trade online and effectively manage a business through the internet means the plans could have a substantial impact on companies in Scotland. Parcel2Go's marketing director Richard Mercer, said the parts of the IAP aimed at improving access to mobile data services could also be hugely beneficial to firms.
He said: "More and more small businesses are coming to rely on the internet and are managing to boost their takings through e-commerce. Parcel2Go helps thousands of these companies find cheap courier deals so they can ship consignments across the world, and from feedback, we understand all too well how important online services have become to the UK's small businesses.
"With Britain facing the possibility of another recession, schemes such as this which will help firms to grow should be made a top priority. It is innovative and dynamic companies that will help Britain move towards an improved economic situation and Britain should be doing everything possible to support that growth."
cheap couriercouriers UKinternational postagePArcel2Go
Parcel2Go backs findings of global parcel delivery survey
The UK's largest online parcel delivery specialist has said it is unsurprised by the results of a recent study highlighting the growing importance of online delivery services.
A worldwide survey of 93 members of the Universal Postal Union showed that 70 per cent believe postal e-services are strategically important for the future. The research identified 55 different types of digital services which are now available, including track and trace and online bill payments.
According to Bolton-based Parcel2Go, which has been involved in helping businesses and individuals to organise international parcel services for over 20 years and is involved with the delivery of more than two millions parcels a year, demand for online services will continue to grow at a rapid rate.
Richard Mercer, marketing director at Parcel2Go, said the simplicity of arranging shipping services through the internet is one of the main appeals.
He said: "The results of the Universal Postal Union survey make interesting reading, but we're not surprised to find that an increasing number of organisations are recognising the potential of online services.
"At Parcel2Go we have been focussed on bringing the latest online services to our customers for many years. Feedback tells us that online tools such as parcel tracking are highly valued by individuals, while for many business customers they have become invaluable."
Richard added that as mobile devices such as tablet computers come to play an increasing part in people's daily lives, demand for online courier services is only going to increase.
The survey put Switzerland at the top of the list in terms of overall e-services development, while the US, Canada and Germany all featured in the top ten. The Universal Postal Union said it was the first time it had surveyed its members on e-services, but added that this type of study will now be conducted on a regular basis.
courier servicesFedExinternational parcelPArcel2GoUK courier service
Send your Valentine's Day gift with care, says Parcel2Go
January 20, 2012 EPR Consumer News	Leave a comment
Organisation is one of those things that many people struggle with, especially men! But Parcel2Go, the UK's largest online parcel delivery company has laid down a challenge to both sexes ahead of Valentine's Day 2012 – get organised and score some serious brownie points.
The online parcel delivery specialist is reminding all couples that with just a matter of days to go until Valentine's Day on February 14, it's vital to get prepared now and make sure that if you are planning something special for a loved one, everything goes to plan. Making grand statements and splashing some cash is always going to be appreciated, but lots of people are feeling the pinch at the moment and small gestures that come from the heart can say just as much as lavish ones.
Richard Mercer, marketing director at Parcel2Go, said: "Surprises are what Valentine's Day is all about, but let's face it, no one wants a nasty surprise, which is why it really does pay to get everything planned well ahead of time.
"Having a gift fail to turn up is the worst possible result, which is why it makes absolute sense to ensure that you make sure your present is being shipped with a reliable courier company."
Many couples won't be able to spend Valentine's Day together for various reasons but that doesn't mean that the man or woman can't make a romantic gesture and let their other half know how much they care. Finding a special gift and organising for it to be delivered with a professional carrier through Parcel2Go's website takes just a few minutes and the range of UK courier services available means there is an option to suit every budget.
Richard added: "The reality is that most people won't change the habit of a lifetime and will end up sending things at the last minute! Thankfully the couriers we work with are highly experienced at delivering packages and meeting deadlines so any last-minute romantics will be able to relax if they send their loved one a gift with the help of Parcel2Go."
courierfed exinternational couriersPArcel2GoUK courier services
Businesses must act to take advantage of tablet computing in 2012, says Parcel2Go
Tablet computing is growing at a rapid rate and businesses in the UK should make sure they're in a position to benefit, according to Britain's largest online parcel delivery service.
Parcel2Go, which helps individuals and businesses send millions of packages to domestic and foreign addresses each year, has urged companies to make the most of the fact that more people are using mobile devices to buy online.
The latest research paper from online analytics consultancy Logan Tod & Co said the sudden emergence of tablets "almost came out of nowhere". Out of the 1,121 adults the company spoke to at the end of last month, 14 per cent said they had used either an iPad or another make of tablet computer to purchase a gift over the Christmas period. Logan Tod & Co said in 2010, 7 per cent of people used a mobile phone to purchase a Christmas gift – that more than doubled to 15 per cent this Christmas.
With more consumers expected to invest in a tablet computer this year, the opportunity for retailers is evident.
Richard Mercer, marketing director at Parcel2Go, said: "This research highlights just how important it is for retailers to adopt a multi-channel approach in order to maximise sales opportunities. Having an online presence is now a must for all companies, regardless of which sector they are in, but taking that a step further and optimising websites for mobile and tablet devices now looks like it will pay dividends.
"Parcel2Go works with many thousands of companies, helping them to ship their goods to customers around the world, and it is clear that demand for well laid out, intuitive websites offering reliable international shipping options is not going to diminish anytime soon."
delivery serviceGlasgow courier serviceinternational shippingPArcel2Goparcelforce
Parcel2Go Boss Calls On People To Unleash Their Entrepreneurial Spirit
The founder of the UK's largest online parcel delivery service, Parcel2Go, has said anyone is capable of making it in business if they have the right attitude.
Fil Adams-Mercer launched the Parcel2Go.com website in 2000 and over the past 11 years has helped build the company into an industry leader, responsible for handling more than two million packages every single year and attracting in excess of 18,000 new customers each month.
Speaking to the Daily Telegraph newspaper, he said he was inspired to launch an online presence following a trip to America, "where every single advert was forwww.something.com". None of the major UK couriercompanies had ventured online and started offering bookings over the internet at this point, and his vision was rewarded with success. Parcel2Go turned over £17.5m in the 12 months to April 2011, a figure which is expected to rise to £22m this year.
But while Mr Adams-Mercer has now earned a respected place as one of the UK's top business leaders, he remains proud of his background and his first job learning how to sell on Bolton Market when he was still at school.
He said: "I don't mind being compared to Del Boy. That's what I am, a market trader done good.
"I don't do joined-up writing and I can't spell for toffee. So doesn't that give everyone a chance? If I've done it, you can do it."
Parcel2Go itself plays a key part in helping entrepreneurs and small businesses get their goods to customers in the UK and countries across the world quickly, efficiently and cheaply with reliable courier services. In recent years an increasing number of start-ups have established themselves online and now rely on world-renowned couriers booked through Parcel2Go to get their consignments delivered safely and on time.
Bristol courier serviceCity Linkcourier servicesPArcel2GoUK courier
Consumer, Consumer Information, Consumer Services, Internet, Reviews, Services
Parcel2Go reminds first-time eBayers to take care when sending off unwanted gifts
December 28, 2011 EPR Consumer News	Leave a comment
Hundreds of thousands of people are likely to go onto the internet over the Christmas period in an attempt to dispose of their unwanted presents. Gifts from aunties and uncles that simply don't cut it will be auctioned off quicker than you can say gift receipt, but online parcel delivery specialist Parcel2Go is warning first-time sellers not to be too hasty.
Last year, eBay estimated that 550,000 people would go onto the internet either on Christmas Day or Boxing Day to sell their unwanted gifts online. New technology such as iPads, laptops and smartphones mean it is easier to get onto eBay than ever before, and the opportunity to get cash for unwanted gifts is likely to appeal to a large number of people this year.
Parcel2Go is urging those people who haven't sold items over the internet before to take their time if they want the process to go smoothly and prevent their Christmas Day celebrations turning into a Boxing Day hangover. The company's marketing director, Richard Mercer, said while the process of listing goods might be very straight forward, there are a few things sellers should remember.
"Making your goods appeal to as wide an audience as possible is very important and can make a significant difference to the amount of interest your auction attracts," he said. "For example, failing to make sure that you offer a range of delivery options such as international shipping through leading courier companies can put off potential buyers.
"It's also vital to ensure that any items you send off are well wrapped and will not become damaged in transit. The last thing a buyer wants is to unwrap their purchase and find that it is broken. This can cause all sorts of problems and so it is much better to do everything possible, such as using quality packaging and a leading UK courier, to avoid such a situation."
international shippingManchester courier serviceparcel deliveryPArcel2GoUK courier
Crescendo Home Theater Opens Location in Los Angeles, Beverly Hills California area
Translation Works Full Review
Make best use of Online Banking and stop wasting time
Tour Operator launches Online Booking for Nairobi City Tours and Luxury Safaris
Roof Crafters Gives Away New Roof
DIRECT CONNECT CONTINUES TO ACQUIRE SALES OFFICES WITH PURCHASE OF FLORIDA ISO
Payless Plumbing Blog offers Free Plumbing Consulting Services to Home-owners
Hands in Motion is pleased to announce the launch of their Video Remote Interpreting (VRI) Service for Deaf and Hard of Hearing consumers and consumers who speak another language nationwide
Leading Personal Property Evaluation Expert Allan Baitcher Provides Aon Insurance Wealth Managers the Tools for Success
Local Venue to Give Away Wedding and Hotel Overnight stay at Gay Lesbian Wedding Expo March 23
Allens Hire teases Event Colour Schemes using Pantone's Colour of the Year
Harvard Grad Becomes Psychic Counselor
PlagiarismExamine declares war against plagiarism
Beauty Beauty Products & Services blair rewards Blairrewards blair rewards membership blair rewards program Business carpet cleaning Clothing Products & Services Consumer Consumer Goods Consumer Information Consumer Products Consumer Services cooker repairs Cosmetic Surgery easy saver cancellations easy saver rewards easysaver rewards FedEx financial Financial Services Gifts & Occasions Harley Medical Group Healthcare Holidays Products & Services Home & Garden Internet Jewelry Products Lifestyle Products loans marriage money PArcel2Go parcel delivery parcelforce parcel tracking postage rates Retail Trade Services Shopping Travel tree planting tree removal world courier
Beauty Products & Services
Clothing Products & Services
Eyewear Products
Holidays Products & Services
Jewelry Products
American Consumer News
CNET Reviews
Consumer World
ConsumerAffairs.com
Consumerist.com
Consumers Union
DigitalConsumer.org
EPR Advertising News
EPR Consumer News @ Feedburner
EPR Consumer News @ MyBlogLog
EPR Consumer News @ Technorati
EPR Marketing News
EPR Media News
EPR Network's Consumer Services press releases
EPR Travel News
EprNetworkBlog
FDIC Consumer News
Federal Citizen Information Center
Free Consumer Press Releases
FTC Bureau of Consumer Protection
Idaho Consumer News
MrConsumer
New Consumer
Oleg Lazarov
Real Time Consumer Press Release Distribution
Reviews from Epinions
Safe Consumer News
Seattle Consumer News
The American Council on Consumer Interests
TheBostonChannel.com | Consumer News
EPR Consumer News and all content & imagery © 2008 - 2020 unless otherwise noted. A division of EPR Network - Press Release Distribution. All Rights Reserved. Proudly powered by WordPress


text:
Most Expensive Homes | Jan 18, 2021
Peek Inside Roger Federer Incredible Mansion with Views to Lake Zurich
Peek Inside Roger Federer Incredible Mansion with Views to Lake Zurich – Tennis ace Roger Federer has £6.5 million glass mansion on the shores of a Swiss lake. The state-of-the-art three-stores building, with a swimming pool and magnificent views stretching across Lake Zurich is an architecture masterpiece.
Published on: Jul 16, 2017
Check the Photo Gallery Bellow >>
Shop the Look:
The liberal tax structure has attracted other multi-millionaires. Formula One drivers Kimi Räikkönen and Felipe Massa and the former UBS chairman Marcel Ospel have all chosen to live in the canton. Federer's home, on a plot of about 1.5 acres with underground parking, is believed to be worth £6.5 million. There is a glass dome over the living area.
In addition to Federer's house there are two luxury apartments, one of which is believed to be for his parents Robert and Lynette.The building is called The Residence and is in Wollerau in canton Schwyz. It has floor-to-ceiling windows and large balconies overlooking the lake.Federer moved from his birthplace of Basel to the tax paradise of Wollerau in March 2008. It is one of the lowest tax municipalities in Europe. It is about 20 minutes from Zurich and an hour's drive to Basel.
See the Gallery:
count(page_images)1
View Slideshow >
The developer, Kamata Development, described the project as "prestigious, contemporary architecture with extensive glazing".
Keep following Celebrity Homes to have the opportunity to be inside celebrity homes and to know the latest celebrity news and celebrity couples news!
Folow Celebrity Homes at Pinterest and Instagram!
Step Inside Althorp Princess Diana's Childhood Home
Celebrity News: Adam Levine and Behati Prinsloo Los Angeles Home
Source: telegraph.co.uk
Most Expensive Homes | Jun 27, 2016
Inside Celebrity Homes: Katharine Hepburn House
Most Expensive Homes | Oct 29, 2016
Lady Gaga Shows Interest in Frank Zappa Home
Most Expensive Homes | Nov 16, 2016
Celebrity Homes: Christmas at White House Through the Years

redpajama_set_name: RedPajamaCommonCrawl


Maximum safety distance: The optional combi-tiller increases the safety distance to the operator, ensuring even greater safety during operation.
The powerful EXU-SF low lift pallet truck from STILL with a hinged platform and a load capacity of up to 2,000 kg is designed for work in very narrow spaces and for transporting goods horizontally.
This compact warehouse helper can be manoeuvred accurately and safely in narrow spaces. All of which makes it the ideal choice for loading and unloading lorries. The truck enables goods to be turned around fast over multiple shifts in the industrial sector and rapid material handling in retail environments. The unique STILL combi-tiller can be folded down to increase speed in pedestrian mode. This means that material can be transported fast with the highest levels of safety. The air suspension on the stand-on platform, which can be individually adjusted to the driver's weight, and the height-adjustable side guards provide a high level of comfort and safety. The precise and intuitive electrical steering unit minimizes operator fatigue. The performance of the EXU-SF can be adapted to the job at hand at the touch of a button: The ECO and BOOST driver programmes allow drivers to choose between maximum performance and maximum efficiency.


To start planning your trip Down Under, call a Bridge The World specialist on 0800 988 6884.
And that's not all; with the Great Barrier Reef, the idyllic Whitsunday Islands, the tropical beaches of Queensland, the rugged Kimberley region and the unspoilt island of Tasmania, there's so much more to explore in Australia. Take a look at our Australia brochure or call us on 0800 988 6884 to find out what other incredible experiences we have to offer.


Research Triangle Park, research, business, medical, and educational complex situated in central North Carolina. It has an area of 6,900 acres (2,795 hectares) and is 8 × 2 mi (13 × 3 km) in size. Named for the triangle formed by Duke Univ. in Durham, the Univ. of North Carolina in Chapel Hill, and North Carolina State Univ. in Raleigh, it is one of the largest research complexes in the United States. The park was created in 1959 by leaders from business and academia; by the late 1990s it was home to nearly 140 organizations, more than a hundred of which were related to research and development, and employed about 50,000 people. Companies represented there engage in high-technology research, development, and manufacturing in such areas as the health sciences, pharmaceuticals, computers, optics, and many other for-profit and nonprofit enterprises. Development of the park, which has no residential facilities, has caused surrounding communities to mushroom and has created some local transportation problems.


Just finished welding in a panel to fill in a recessed license plate. Was trick in 1970, but now past its time. Body is ready to be pulled from the frame, body will go back on the roto - to start the paint process, which will be a long process..
I wonder what it would be like to get one of those engines in a Tercel4wd. that would be an interesting project, the whole drive train and suspension would have to be upgraded along with the engine.
My plans are to put a '96 LS 400 engine im my 1983 Tercel 4wd I bought from Texas, it won't be 4WD anymore, just RWD. I bought a smasshed LS 400 and a smashed never winter driven California '84 Supra for the transmission and rear differential. Should be quite a little sleeper, leaving it all completely stock looking. I could put a small block Chev or Ford engine in it a lot easier but I want to keep it 100% Toyota. I know Petro, you're going to say, "Don't do that to a perfecly mint all original 4wd SR5 wagon",but I just have too, it will still be COMPLETELY STOCK (Looking) I promise.
well, I would say if you can keep it 4wd, GO FOR IT. the 4wd feature is best thing about an otherwise common '80s econobox. More power and eliminating the carburatred engine is a big improvement. You will also find that with that much power and weight increase, you will also have to do some serious suspension upgrades. Bigger tires too, to keep all that power on the road. that might mean some cutting and welding of the fender wells to gain some room.
I will egarly await to see that transformation. find some way to keep the 4wd feature, perhaps adapt a 4wd truck transmission and front drive train, or find a way to shoe horn in an all-trac Camry drive train.
I plan on using the whole front suspension from the Supra, the part on the Tercel wher the front control arms bolt on are just spot welded on to the frame rails so once I remove them I can use the Supra cross member which has the control arms attached to it, granted there is going to be some massaging in some spot, but not that much. I have two parts cars that have to go to the scrap yard but I'm keeping the engine compartment off one of them, that way I'll use it as a pattern so I don't have to cut places and reweld the good Terc when I put the drivetrain in it.
I am in awe of both, whether hands-on or self-driven.
A few more pix of the progress, it moves along slowly each day.


text:
IL-12 Enhances CD8 T Cell Homeostatic Expansion
William C. Kieper, Martin Prlic, Clint S. Schmidt, Matthew F. Mescher and Stephen C. Jameson
J Immunol May 1, 2001, 166 (9) 5515-5521; DOI: https://doi.org/10.4049/jimmunol.166.9.5515
William C. Kieper
Department of Laboratory Medicine and Pathology, University of Minnesota Center for Immunology, Minneapolis, MN 55455
Martin Prlic
Clint S. Schmidt
Matthew F. Mescher
Stephen C. Jameson
The size of the T lymphocyte pool is maintained by regulation of T cell production, proliferation, and survival. Under the pressure of a T lymphopenic environment, mature naive T cells begin to proliferate in the absence of Ag, a process called homeostatic expansion. Homeostatic expansion involves TCR recognition of self peptide/MHC ligands, but less is known about the soluble factors that regulate this process. Here we show that IL-12 dramatically enhanced the homeostatic proliferation of CD8 T cells. In contrast, IL-2 had no beneficial effect on homeostatic expansion and, in fact, inhibited T cell expansion induced by IL-12. Using gene-targeted mice, we showed that IL-12 acted directly on the T cells to enhance homeostatic expansion, but that IL-12 cannot override the requirement for TCR interaction with self peptide/MHC ligands in homeostatic expansion. These data indicate that inflammatory cytokines may modulate T cell homeostasis after lymphopenia and have implications for regulation of the T cell repertoire and autoimmunity.
Recent data have shown that restoration of normal T cell numbers in a lymphopenic animal involves the proliferation of naive T cells. This process, called homeostatic expansion, does not involve Ag recognition, but nevertheless requires TCR recognition of self peptide/MHC ligands (1, 2, 3, 4, 5, 6, 7). Some groups have suggested that the same self-peptide/MHC ligands required for thymic-positive selection are also important for homeostatic expansion in the periphery (1, 2, 8, 9), although other reports argue against this correlation (10). Indeed, there is some evidence that homeostatic expansion can occur (albeit more slowly) even in the absence of a conventional TCR ligand (11). These data suggest that other factors beyond the TCR are involved in homeostatic expansion.
Accumulating evidence indicates that cytokines play a critical role in driving homeostatic expansion. We have shown that there is a critical role for IL-7 in CD8+ T cell homeostatic expansion and survival (12), in keeping with the pivotal role of this cytokine at multiple stages of T cell life (13, 14). In contrast, IL-2, which dominates regulation of Ag-driven T cell responses, has been reported not to be required for homeostatic expansion (6), although the impact of exogenous IL-2 on homeostatic expansion has yet to be reported. Thus, the role of cytokines in homeostatic expansion vs Ag-driven activation are notably different.
Here we study the impact of supplementary cytokines on CD8 T cell homeostatic expansion. Two cytokines with well-documented effects on CD8 T cell proliferation and differentiation were tested: IL-2 and IL-12. Although IL-2 is a prototypic T cell growth factor, the proinflammatory cytokine IL-12 is implicated in augmenting both CD8 T cell growth and differentiation (15, 16, 17, 18, 19). Indeed, recent evidence indicates IL-12 can provide a critical third signal, along with Ag and IL-2, to activate naive CD8 T cells in vitro (18) and has an adjuvant-like effect in activating CD8 T cell responses to peptide Ag in vivo (19). We report here that IL-12, but not IL-2, enhances homeostatic expansion, leading to amplification of functional T cells. The response to IL-12 is evidently T cell autonomous, because it has its effects even when IL-12R expression is exclusively on the T cells. These data argue that cells undergoing homeostatic expansion are receptive to the proinflammatory cytokine IL-12, and that this factor can modify the size, phenotype, and reactivity of the homeostatically expanded pool.
OT-I TCR transgenic mice and OT-I.PL mice (expressing the Thy1.1 allele) have been described previously (4, 20). Mice deficient in IL-12 p40 subunit (IL-12o/o), IL-12R β1 subunit (IL-12Rco/o), and recombinase-activating gene-1 (RAG-1o/o) were obtained from The Jackson Laboratory (Bar Harbor, ME) and were maintained in specific pathogen-free conditions throughout the experiments. Some mice were subjected to sublethal irradiation (700 rad) 1–2 days before T cell transfer. Some mice were thymectomized, allowed to recover (for at least 2 wk), and then sublethally irradiated at least 2 wk before adoptive transfer.
All thymectomized and irradiated mice were maintained on antibiotic water (polymixin B sulfate and neomycin sulfate) and under specific pathogen-free conditions throughout the course of the experiment.
Recombinant mouse IL-12 was obtained from Genetics Institute (Cambridge, MA), and recombinant mouse IL-2 was obtained from R&D Systems (Minneapolis, MN). Cytokines were injected i.p. on days 1, 2, and 3 post-T cell transfer with IL-12 (1 μg, equivalent to 2700 ± 1200 U) and IL-2 (2000 IU/injection), as used previously (19, 21). Cytokines were injected in 100 μl of PBS with 1% mouse serum, and this vector was also used as the control.
Adoptive transfer
Single-cell suspensions were prepared from lymph nodes of donor mice and CD8+ T cells (from OT-I or OT-I-Thy1.1 donor animals) or total T cells (from normal C57BL/6 donors). T cell purification (by negative selection) involved Cellect columns (Cytovax Biotechnologies, Edmonton, Canada) or magnetic cell sorting using MACS microbeads (Miltenyi Biotec, Auburn, CA). For OT-I, the purification was through elimination of CD4 T cells and B cells. For normal B6 donors, only B cells were eliminated. The purity of the T cells ranged from 85 to 95% pure (established by flow cytometric analysis). In some cases naive (CD44low) OT-I CD8 cells were purified. OT-I lymph node cells were depleted of adherent cells (90-min incubation on tissue culture-treated flasks at 37°C) and labeled with FITC-coupled anti-B220, CD4, and CD44 (all obtained from PharMingen, San Diego, CA) Abs (0.125 μg of anti-B220 and CD4/1 × 106 cells, 0.04 μg of anti-CD44/1 × 106 cells). Anti-FITC microbeads (Miltenyi Biotec) were used to negatively select CD44low, CD8 cells with the MACS system. Cells were >95% pure (established by flow cytometric analysis).
Cells were labeled before or after purification with CFSE (Molecular Probes, Eugene, OR) essentially as previously described (4, 22). Briefly, pooled lymph node cells were suspended at a concentration of 1–5 × 107/ml in HBSS. After warming to 37°C, CFSE was added at a concentration of 0.5–5 μM for 10 min with occasional mixing, followed by addition of ice-cold RPMI medium containing 10% serum and cell recovery by centrifugation. Purified donor cells were suspended in PBS and injected i.v. into the tail vein of recipient mice. During multiple experiments 1–3 million cells were injected into irradiated recipients, and 1–5 million were injected into unirradiated recipients. Similar results were obtained regardless of the transferred cell number.
In some cases mice were immunized with OVA peptide (OVAp),4 with or without injection of IL-12 treatment. OVAp was given as two injections (25 μg of peptide/injection) administered s.c. on the lower and upper back on day 14 only. IL-12 (1 μg/injection) and PBS were given i.p. on days 14, 15, and 16, and the mice were harvested on day 17.
Recipient mice were sacrificed at the time points indicated, and single-cell suspensions were prepared separately from spleen and a pool of major lymph nodes. Lymph node and spleen cells were then stained with combinations of the following Abs: anti-CD8 conjugated to PE or allophycocyanin, anti-Thy1.1-bio, anti-CD44-PE, anti-CD4-allophycocyanin, or anti-Thy1.1-PerCP and followed with either streptavidin-TriColor or streptavidin-PerCP (all obtained from PharMingen). The cells were analyzed with a Becton Dickinson FACSCalibur (Mountain View, CA) using both CellQuest (Becton Dickinson) and FLOWJO (TreeStar, San Carlos, CA) software.
CTL killing assay
The cytolytic potential of cells was tested in a 51Cr release assay, essentially as previously described (23). Briefly, EL4 tumor cells were labeled with [51Cr]sodium chromate with or without the addition of 10 μM OVAp. OT-I.PL cells were recovered from lymph nodes of adoptively transferred (Thy 1.2) hosts by positive selection over magnetic columns after staining the cells with anti-Thy1.1 Abs (2.5 μg of HIS51-bio Ab/1 × 107 cells) and streptavidin-conjugated microbeads (Miltenyi Biotech). Target cells were washed and incubated with titrated numbers of effector cells in a 4-h assay. Percentages of OT-I cells in the effector population were calculated from flow cytometric analysis of a sample of the lymph node preparation, and the data are presented as adjusted E:T cell ratios to reflect this calculation. Lysis on EL4 cells without OVAp was <5%
Exogenous IL-12 directly enhances naive CD8 T cell homeostatic expansion
OT-I transgenic CD8 T cells were adoptively transferred into irradiated wild-type B6 recipients. The recipients received injections of PBS, IL-2, IL-12, or a combination of IL-2 plus IL-12, and the impact on OT-I homeostatic expansion was monitored by CFSE dye dilution and by the total cell numbers of the transferred cells.
Exogenous IL-12 greatly enhanced OT-I proliferation, as measured by CFSE dilution (Fig. 1⇓A) and by total number of OT-I T cells recovered from lymph node (Fig. 1⇓B). In contrast, we observed no effect on OT-I homeostatic expansion of supplementary IL-2 alone (Fig. 1⇓). However, supplementary IL-2 did change the response to IL-12; coinjection of IL-12 plus IL-2 resulted in less accumulation of OT-I cells than IL-12 administration alone (Fig. 1⇓B) and a slight reduction of proliferation (Fig. 1⇓A). The basis by which IL-12 might alter sensitivity to IL-2 is addressed later.
Effects of IL-2, IL-7, and IL-12 on homeostatic proliferation. CD8+ T cells were purified from OT-I.PL donors, labeled with CFSE, and transferred into irradiated C57BL6 recipients. On days 1, 2, and 3 post-transfer the recipients received i.p. injections of PBS, IL-2 (2000 IU/day), or IL-12 (1 μg/day). Lymph nodes and spleens were harvested from recipients on day 7 post-transfer and analyzed by FACS for both CFSE expression (A) and total cell numbers (B; with SD shown as error bars). The data presented here are gated on live Thy1.1+/CD8+ T lymphocytes obtained independently from the lymph nodes of three mice per condition and are representative of two independent experiments.
Because IL-12 is well known to stimulate NK cells as well as T cells (15), it was important to test whether the IL-12 acted directly on the OT-I T cells or indirectly via stimulation of host cells. To differentiate between these two possibilities, we studied the effect of exogenous IL-12 on OT-I homeostatic expansion in both wild-type and IL-12-Rcβ1-deficient (24) hosts. In the latter recipients, host T and NK cells are unable to respond to IL-12 (24), and thus only the donor OT-I cells would be able to respond to its presence. As shown in Fig. 2⇓, IL-12 augmented the proliferation of OT-I cells in both host strains (Fig. 2⇓), arguing that the OT-I CD8 T cells themselves are receptive to IL-12 signals during homeostatic expansion. This complements previous data, indicating that IL-12 can support CD8+ T cell responses to antigenic stimulation (18, 19), and suggests that IL-12 has a similar effect on homeostatic expansion.
IL-12 can increase homeostatic proliferation by acting directly on the T cells themselves. Purified OT-I.PL, CD8+ T cells were CFSE labeled and adoptively transferred into irradiated C57BL6 and IL-12R-deficient recipients. Recipient mice were injected with PBS (thick, unfilled line) or IL-12 (thin, gray-filled lines) and analyzed on day 7 after transfer as described in Fig. 1⇑. CFSE levels (A) and total cell numbers (B) in the OT-I donor population were calculated and displayed as described in Fig. 1⇑.
It was possible that the increased proliferation induced by IL-12 was due to expansion of a small population of activated or memory OT-I cells in the inoculum; this is especially concerning because IL-12R is not expressed on resting naive T cells but is up-regulated after TCR stimulation (15, 25). To test this we purified naive phenotype (i.e., CD44 low) CD8+ OT-I cells before adoptive transfer (Fig. 3⇓A). This approach efficiently purifies phenotypically and functionally naive CD8 T cells (1, 18, 19). Once again, we found that IL-12 augmented the homeostatic expansion of these OT-I cells (Fig. 3⇓B), arguing that the effect of IL-12 is mediated on cells that were naive phenotype at transfer.
IL-12 stimulates homeostatic proliferation of CD44low OT-1-Thy1.1 CD8 cells. A, Level of CD44 expression on CD8 T cells before (thin, gray-filled line) and after (thick, unfilled line) purification of CD44low cells via MACS column. B, Purified OT-I-Thy1.1, CD44low, CD8+ T cells were CFSE labeled and adoptively transferred into irradiated C57BL6 mice. Recipient mice were injected with either PBS (thick, unfilled line) or IL-12 (thin, gray-filled line) and analyzed on day 7 after transfer as described in Fig. 1⇑. The data shown are representative for three mice analyzed in each group.
IL-12 in the absence of class I MHC has no effect on homeostatic proliferation
Previous reports have indicated that in order for T cells to respond to IL-12 they must have also received a signal through their TCR (15, 25, 26, 27). In contrast, there is evidence from some groups that homeostatic expansion can occur in the absence of a peptide/MHC ligand for the TCR (11). To test whether the IL-12 effect we observed was dependent on a TCR signal derived from interactions with self-peptide/MHC complexes, we tested the impact of IL-12 on OT-I proliferation after transfer into irradiated B6 or TAP-1o/o recipients. In the OT-I system, the lack of class I MHC expression due to the TAP-1 mutation severely limits homeostatic expansion (2, 4). As expected, IL-12 enhanced proliferation in the B6 hosts (Fig. 4⇓A). Strikingly, IL-12 failed to increase proliferation in the TAP-1o/o hosts environment lacking self-peptide/MHC (Fig. 4⇓A). Indeed, if anything the low grade proliferation we observed in TAP-1 hosts was slightly reduced in the presence of supplementary IL-12. These observations are also directly reflected in the total number of OT-I cells found in the recipients (Fig. 4⇓B). Thus, it appears that T cell sensitivity to IL-12 during homeostatic proliferation first requires a signal through the TCR.
Requirement of self-peptide/MHC interactions for the IL-12 effect. CD8+ T cells were purified from an OT-I.PL donor, labeled with CFSE, and transferred into irradiated B6 or TAPo recipients. The mice were injected with PBS (thick, unfilled line) or IL-12 (thin, gray-filled line) and analyzed on day 7 after transfer as described in Fig. 1⇑. CFSE levels (A) and total cell numbers (B) in the OT-I donor population were calculated and displayed as described in Fig. 1⇑. These data are representative of two independent experiments.
Impact of IL-12 on functional and phenotypic features of cells undergoing homeostatic expansion
Numerous groups have reported that homeostatic expansion involves not only the proliferation of naive T cells, but also their differentiation into memory phenotype cells (1, 2, 3, 4, 5, 6, 7). In contrast to Ag reactivity, this transition appears not to involve a typical effector cell stage, as judged by the classic up-regulation of activation markers (such as CD69 and CD25), and at least for CD8 cells, their functional activity is more similar to that of memory cells than to that of effector cells (1, 2, 3, 4, 5, 6, 7). Because IL-12 can greatly enhance effector differentiation of CD8 T cells in response to Ag (15, 16, 18, 19), we sought to determine whether IL-12 changed the functional or phenotypic characteristics of OT-I cells undergoing homeostatic expansion.
OT-I cells were adoptively transferred into thymectomized/irradiated B6 recipients (mice were thymectomized to avoid host reconstitution of the T cell compartment after irradiation). Two weeks post-transfer the mice were challenged with PBS alone, IL-12 alone, OVAp alone, or a combination of OVAp and IL-12. At this time point virtually all the transferred cells had undergone at least one round of division (data not shown). Homeostatically expanded cells proliferated efficiently in response to both free OVAp alone and OVAp/IL-12 (Fig. 5⇓), suggesting that they are not anergic. There was a greater increase in total cell number of OT-I lymphocytes stimulated with OVAp/IL-12 as opposed to OVAp alone (Fig. 5⇓), in keeping with data showing that IL-12 can act as an efficient adjuvant for CD8+ T cell activation (19). Hence we can conclude that OT-I cells that have undergone homeostatic proliferation not only can respond to Ag (OVAp), but this response can also be further augmented by inflammatory cytokines (IL-12). Note that at this early time point (3 days) after initiating IL-12 administration, there is no effect on OT-I expansion in the absence of Ag. However, similar experiments in which mice were analyzed 7 days after starting IL-12 injections showed that proliferation of OT-I cells is still enhanced by IL-12 (data not shown), implying that reactivity to IL-12 is maintained throughout homeostatic expansion. We also tested the functionality of OT-I cells undergoing homeostatic expansion by performing an ex vivo cytolytic assay. OT-I cells that had undergone homeostatic expansion in irradiated hosts were poor effector cells (Fig. 6⇓), as demonstrated previously (2, 4). Supplementary IL-12 alone did not improve cytolytic effector function (Fig. 6⇓). However, in vivo antigenic stimulation of the OT-I cells generated potent cytolytic effectors, and this was further enhanced by IL-12 (Fig. 6⇓). These data suggest that OT-I cells undergoing homeostatic expansion are not efficient killer cells, but can differentiate into effector cells in response to true antigenic challenge.
Homeostatic proliferation does not render cells anergic to Ag. CFSE-labeled OT-I.PL cells were transferred into irradiated, thymectomized B6 recipients. Fourteen days post-transfer recipient mice received PBS, IL-12, OVAp, or a combination of OVAp and IL-12, as indicated. OVAp was given as two injections (25 μg of peptide/injection) administered s.c. on the lower and upper back on day 14. IL-12 (1 μg/injection) and PBS were given i.p. on days 14, 15, and 16, and the mice were harvested on day 17. Live Thy1.1+/CD8+ cells (donor cells) were analyzed for CFSE levels (A) and cell numbers (B) in the lymph node. Data in B show average cell number (and SD) for three mice per group from one experiment. The data are representative of three to six recipients per condition from two independent experiments.
Homeostatically expanded OT-I become effective killers in response to Ag stimulation. Lymph node cells from three recipient mice per condition, as described in Fig. 5⇑, were pooled and purified for Thy1.1+ expression using positive selection over magnetic columns. The ability of the resulting cells to lyse OVAp-pulsed EL4 target cells was tested in a 51Cr release assay, and the data are represented as the percent specific lysis. The E:T cell ratios shown are corrected for the percentage of cells positive for Thy1.1 and CD8 (i.e., OT-I donor cells) after magnetic purification. Lysis on EL4 without OVAp was <5%.
Finally, the phenotype of OT-I cells undergoing homeostatic expansion in the presence or the absence of IL-12 was addressed. Previous work has shown that CD8 T cells up-regulate CD44, but not CD69 or CD25, during homeostatic expansion (2, 7). As shown in Fig. 7⇓, we found that IL-12 enhances the expression of CD44 even further, with CD44 expression correlating with multiple rounds of division. In contrast, CD69 remains low during homeostatic expansion regardless of the presence of IL-12. CD25 (IL-2R α-chain) is also low on OT-I cells undergoing homeostatic expansion in the absence of IL-12, but, interestingly, CD25 is up-regulated in the presence of IL-12 (Fig. 7⇓). CD25 expression was modest, however, and increased only after around seven or eight cell divisions. In contrast, CD25 was rapidly up-regulated to high levels in the OT-I response to OVAp (data not shown), consistent with the reports of others (5).
IL-12 induces expression of CD25 and increases expression of CD44 during homeostatic expansion. OT-I.PL cells were labeled with CFSE and transferred into unirradiated B6 hosts or into irradiated B6 hosts that were injected with PBS or IL-12 on days 1, 2, and 3 after transfer, as indicated. On day 8 following transfer, the lymph node Thy1.1+ CD8+ population (donor OT-I cells) was analyzed. A, CFSE levels for OT-I cells from unirradiated hosts (black filled line) or from irradiated hosts treated with PBS (gray filled line) or with IL-12 (thick unfilled line) are shown. The numbers represent the number of cell divisions, judged by CFSE dilution. B, The expression of CD25, CD69, and CD44 is plotted vs CFSE for the indicated populations (control indicates cells recovered from unirradiated hosts). Representative data are shown. In this experiment two animals per group were studied with similar results, and the data are also representative of a second experiment when CD44low (i.e., naive phenotype) OT-I cells were used for transfer.
Endogenous IL-12 augments, but is not required for, homeostatic expansion
Because IL-12 is induced only during inflammatory responses rather than constitutively, it seemed unlikely that IL-12 would play a central role in normal T cell homeostatic expansion. In contrast, we and many other groups make extensive use of sublethal irradiation as a means of generating lymphopenic hosts, and it is known that irradiation can induce the production of a variety of inflammatory mediators (28). Therefore, we tested the requirement for endogenous IL-12 in driving homeostatic expansion in irradiated hosts. OT-I cells were tested for their ability to proliferate in irradiated wild-type vs IL-12o/o hosts. As shown in Fig. 8⇓, OT-I cells proliferated less (by two or three rounds of division) in the IL-12-deficient recipients compared with the control recipients, although there was still clearly a robust proliferative response. IL-23, a cytokine that shares certain functions with IL-12, was recently reported (29). Because this cytokine assembles with the p40 subunit of IL-12 (the chain ablated in the IL-12o/o animals used here), we cannot currently determine whether this mild reduction in homeostatic expansion in the IL-12 p40o/o hosts is due to a loss of IL-12 or IL-23. In any case, these data suggest that IL-12 and/or IL-23 may play an important, but not essential, role in driving homeostatic expansion.
Endogenous IL-12 augments CD8 T cell homeostatic expansion. CD8+ T cells were isolated from OT-I.PL donors, labeled with CFSE, and transferred into irradiated B6 (thin, gray-filled line) or irradiated IL-12o/o (thick, unfilled line) recipients. The profiles presented here are gated on Thy1.1+/CD8+ cells and are representative of control (n = 3) and IL-12o/o (n = 4) hosts.
The mature T cell pool is maintained at a fairly constant level by the balance of production, survival, expansion, and death. Recently, studies of T cell homeostasis went in an unexpected direction, with the finding that mature naive T cells proliferate and undergo transient maturation into memory cells upon exposure to self peptide/MHC ligands in a lymphopenic environment (1, 2, 3, 4, 5, 6, 7). This response seems to be important for maintenance of the T cell compartment, but little is known about how homeostatic expansion is regulated.
TCR engagement is important for homeostatic expansion, but this appears to be an interaction with self rather than foreign or environmental peptide/MHC Ags (1, 2, 4, 6, 8). Furthermore, preliminary data suggested that homeostatic expansion does not follow the same rules as typical antigenic stimulation. For example, T cells undergoing homeostatic expansion do not up-regulate normal early activation markers (including CD69 and CD25), and the response does not appear to require the classic costimulator molecule CD28 (1, 6) (M. Prlic and S. C. Jameson, unpublished observations).
To determine what role cytokines play in driving homeostatic expansion, we studied the impact of supplementary IL-2 and IL-12 on this process. IL-2 is known to have multiple effects on T cell expansion and survival; in some cases it may augment the T cell proliferative response and in other cases may blunt it (30, 31). In our experiments we observed no impact of IL-2 alone; this is in keeping with other reports that homeostatic expansion occurs normally using IL-2-deficient T cells (6). Furthermore, these data may be explained by the lack of up-regulation of CD25, the IL-2R α-chain, during homeostatic expansion (2, 5, 6, 7, 32).
Recent evidence has shown that naive CD8 T cells do not differentiate fully when stimulated with Ag plus IL-2/costimulation, but that they also require a third signal that can be provided by adjuvants or IL-12 (18, 19). Thus, in vivo administration of peptide alone can tolerize Ag-specific CD8 T cells (18), while coadministration of peptide and IL-12 supports clonal expansion, differentiation, and development of a memory population (19). We found that IL-12 also augmented CD8 homeostatic expansion, as reflected both by more rounds of proliferation and by increased numbers of donor T cells in secondary lymphoid organs. Previous reports have indicated that for T cells to respond to IL-12 they must have also received a signal through their TCR (15, 25, 26, 27). This also appears to be true in the case of homeostatic expansion, because we saw no effect of IL-12 on OT-I proliferation of survival in (class I-deficient) TAP-1o/o hosts. Thus, we reach the intriguing conclusion that homeostatic expansion appears to be maximal upon signal 1 (TCR ligation, in this case by self peptide/MHC) and signal 3 (in the form of IL-12), but does not require conventional signal 2, as evidenced by the lack of a requirement for IL-2 or classic costimulator molecules (1, 6) (M. Prlic and S. C. Jameson, manuscript in preparation).
Taken together our data indicate that homeostatic expansion involves an atypical pattern of cytokine reactivity, in that T cells develop reactivity to one inflammatory cytokine (IL-12) but not another (IL-2). In contrast, reactivity to both these cytokines is typical of CD8 and Th1 T cells after Ag-driven proliferation (26, 30, 31, 33). As has been previously observed, the poor reactivity to IL-2 is evidently due to lack of up-regulation of CD25 (IL-2Rα) (2, 5, 6, 7, 32). Interestingly, we found that IL-12 administration did increase the expression of CD25 (Fig. 7⇑). This might account for our finding that IL-2 can influence homeostatic expansion when IL-12 is coinjected (Fig. 1⇑). In this case, though, IL-2 appears to induce the loss of OT-I cells after homeostatic expansion rather than their expansion; the basis for this is currently uncertain, but there is considerable evidence that IL-2 not only promotes T cell growth, but also induces activated and memory T cell death (30, 31, 34).
Our previous work indicated that IL-7 plays a critical role in T cell homeostatic expansion (12). This supports earlier reports showing that depletion of IL-7 (together with IL-4) resulted in a loss of naive CD4 T cells (35). In our hands, supplementary IL-7 did not enhance OT-I homeostatic expansion (W. C. Kieper and S. C. Jameson, data not shown). Although this result suggests that endogenous IL-7 may be at saturating levels for homeostatic expansion, it is possible that the IL-7 doses used in these experiments (250 ng/day for 3 days following T cell transfer) were simply too low to affect expansion; this possibility is currently being explored. Together these data argue that endogenous IL-7 is both necessary and sufficient for T cell homeostatic proliferation and mature T cell survival. The role of IL-7 in homeostatic expansion is hard to determine, because IL-7 is a T cell survival factor (13, 35, 36, 37) but can also support T cell proliferation (38, 39). IL-12 has been shown to enhance CD8 T cell expansion and memory cell production during an immune response in vivo (19). Thus, at present it is unclear whether IL-7 and IL-12 act sequentially or cooperatively in driving homeostatic expansion, a question that will require further investigation. Dissecting the roles of these cytokines on simple T cell survival vs enhanced T cell reactivity will be important to understand the regulation of homeostatic expansion and the potential for its therapeutic manipulation.
There is less information on the factors that might oppose homeostatic expansion. Our data argue that high dose IL-2 can counter the enhancing effect of IL-12 on OT-I homeostatic expansion, leading to a loss of T cell accumulation (Fig. 1⇑). This ties in with previous work suggesting that IL-2 can restrain as well as promote T cell proliferation (31, 40, 41, 42, 43), and more specifically, that IL-2 can lead to loss of memory phenotype CD8 T cells (34). Furthermore, data from two groups demonstrated that T cell expression of a dominant-negative TGF-β receptor resulted in the massive expansion of CD8+ lymphocytes (44, 45). Although the constellation of activation/memory markers induced on these cells is not identical with that on cells undergoing homeostatic expansion, it is tempting to speculate that TGF-β (which is constitutively expressed) may dampen homeostatic expansion. Interestingly, studies on Ag-driven T cell responses suggest that TGF-β and IL-12 oppose each others' functions (46, 47, 48, 49). Thus, the balance between these cytokines (and presumably others) may determine the occurrence and extent of homeostatic expansion.
Chronic antigenic stimulation of T cells can lead to functional unresponsiveness toward a subsequent Ag challenge, especially in the absence of costimulation or "danger" cues (50, 51). Because homeostatic proliferation occurs in response to a continual presence of self-peptide/MHC ligands and does not appear to involve classic costimuli (1, 6), it was possible that homeostatic expansion would generate anergic T cells. Hence another important aspect of our experiments is the finding that OT-I CD8 T cells that had undergone homeostatic expansion are fully capable of responding to Ag stimulation both by proliferation and by in vivo differentiation to cytolytic effector cells (Figs. 5⇑ and 6⇑). Significantly, the process of homeostatic expansion apparently allows these T cells to respond to peptide Ag without adjuvant (evidenced by the proliferative and differentiative response seen to OVAp alone; Figs. 5⇑ and 6⇑). In contrast, previous work indicated that naive CD8 T cells were anergized by peptide Ag alone and required an adjuvant (such as CFA or IL-12) that was absolutely required for effector cell differentiation (18, 19). More recent work has shown that memory CD8 T cells differ in this requirement for adjuvant, and can respond to peptide alone (C. S. Schmidt and M. F. Mescher, manuscript in preparation). Overall, then, our data support the finding of others that homeostatic expansion produces competent cells with memory function.
Homeostatic expansion has some elements of autoimmunity, in that it involves overt reactivity of T cells to self peptide/MHC ligands, accompanied by proliferation and differentiation. Indeed, in reference to our current data it is noticeable that the pathogenesis of several autoimmune diseases involves IL-12 (52, 53, 54, 55). Because there is extensive evidence that recovery from lymphopenia can induce autoimmune diseases (56, 57, 58, 59), it will be interesting to determine whether IL-12 can exacerbate autoimmunity through its effect on T cell homeostatic expansion.
We thank Paul Weaver and Javier Valenzuela for technical advice, and Kris Hogquist, Marc Jenkins, and members of the Jameson and Hogquist laboratories for helpful discussions. Recombinant IL-12 was kindly provided by Genetics Institute.
↵1 This work was supported by Grant RPG-99-264 from the American Cancer Society and National Institutes of Health Grant AI38903 (to S.C.J.), and a predoctoral fellowship from National Institutes of Health Immunology Training Grant T32 AI07313 (to W.C.K.).
↵2 Current address: Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
↵3 Address correspondence and reprint requests to Dr. Stephen C. Jameson, University of Minnesota Medical Center, MMC 334, 420 Delaware Street SE, Minneapolis, MN 55455. E-mail address: james024{at}tc.umn.edu
4 Abbreviation used in this paper: OVAp, OVA peptide.
Accepted February 27, 2001.
Ernst, B., D.-S. Lee, J. M. Chang, J. Sprent, C. D. Surh. 1999. The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. Immunity 11: 173
Goldrath, A. W., M. J. Bevan. 1999. Low-affinity ligands for the TCR drive proliferation of mature CD8+ T cells in lymphopenic hosts. Immunity 11: 183
Oehen, S., K. Brduscha-Riem. 1999. Naive cytotoxic T lymphocytes spontaneously acquire effector function in lymphocytopenic recipients: a pitfall for T cell memory studies?. Eur. J. Immunol. 29: 608
Kieper, W. C., S. C. Jameson. 1999. Homeostatic expansion and phenotypic conversion of naive T cells in response to self peptide/MHC ligands. Proc Natl Acad Sci USA 96: 13306
Goldrath, A. W., L. Y. Bogatzki, and M. J. Bevan. 2000. Naive T cells transiently acquire a memory-like phenotype during homeostasis-driven proliferation. J. Exp. Med. 192:4:557.
Cho, B. K., V. P. Rao, Q. Ge, H. N. Eisen, and J. Chen. 2000. Homeostasis-stimulated proliferation drives naive T cells to differentiate directly into memory T cells. J. Exp. Med. 192:4:549.
Murali-Krishna, K., and R. Ahmed.2000. Cutting edge: naive T cells masquerading as memory cells. J. Immunol. 165:4:1733.
Viret, C., F. S. Wong, C. A. J. Janeway. 1999. Designing and maintaining the mature TCR repertoire: the continuum of self-peptide:self-MHC complex recognition. Immunity 10: 559
Witherden, D., N. van Oers, C. Waltzinger, A. Weiss, C. Benoist, D. Mathis. 2000. Tetracycline-controllable selection of CD4+ T cells: half-life and survival signals in the absence of major histocompatibility complex class II molecules. J. Exp. Med. 191: 355
Bender, J., T. Mitchell, J. Kappler, P. Marrack. 1999. CD4+ T cell division in irradiated mice requires peptides distinct from those responsible for thymic selection. J. Exp. Med. 190: 367
Clarke, S. R., A. Y. Rudensky. 2000. Survival and homeostatic proliferation of naive peripheral CD4+ T cells in the absence of self peptide:MHC complexes. J. Immunol. 165: 2458
Schluns, K. S., W. C. Kieper, S. C. Jameson, L. Lefrancois. 2000. Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat. Immunol. 1: 426
Marrack, P., T. Mitchell, J. Bender, D. Hildeman, R. Kedl, K. Teague, J. Kappler. 1998. T-cell survival. Immunol. Rev. 165: 279
Hofmeister, R., A. R. Khaled, N. Benbernou, E. Rajnavolgyi, K. Muegge, S. K. Durum. 1999. Interleukin-7: physiological roles and mechanisms of action. Cytokine Growth Factor Rev. 10: 41
Trinchieri, G.. 1995. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu. Rev. Immunol. 13: 251
Gajewski, T. F., J. C. Renauld, A. Van Pel, T. Boon. 1995. Costimulation with B7-1, IL-6, and IL-12 is sufficient for primary generation of murine antitumor cytolytic T lymphocytes in vitro. J. Immunol. 154: 5637
Fallarino, F., C. Uyttenhove, T. Boon, T. F. Gajewski. 1996. Endogenous IL-12 is necessary for rejection of P815 tumor variants in vivo. J. Immunol. 156,3: 1095
Curtsinger, J. M., C. S. Schmidt, A. Mondino, D. C. Lins, R. M. Kedl, M. K. Jenkins, M. F. Mescher. 1999. Inflammatory cytokines provide a third signal for activation of naive CD4+ and CD8+ T cells. J. Immunol. 162: 3256
Schmidt, C. S., M. F. Mescher. 1999. Adjuvant effect of IL-12: conversion of peptide antigen administration from tolerizing to immunizing for CD8+ T cells in vivo. J. Immunol. 163: 2561
Hogquist, K. A., S. C. Jameson, W. R. Heath, J. L. Howard, M. J. Bevan, F. R. Carbone. 1994. T cell receptor antagonist peptides induce positive selection. Cell 76: 17
Shrikant, P., A. Khoruts, M. F. Mescher. 1999. CTLA-4 blockade reverses CD8+ T cell tolerance to tumor by a CD4+ T cell- and IL-2-dependent mechanism. Immunity 11: 483
Kurts, C., H. Kosaka, F. R. Carbone, J. F. Miller, W. R. Heath. 1997. Class I-restricted cross-presentation of exogenous self-antigens leads to deletion of autoreactive CD8(+) T cells. J. Exp. Med. 186: 239
Jameson, S. C., M. J. Bevan. 1992. Dissection of major histocompatibility complex (MHC) and T cell receptor contact residues in a Kb-restricted ovalbumin peptide and an assessment of the predictive power of MHC-binding motifs. Eur. J. Immunol. 22: 2663
Wu, C., J. Ferrante, M. K. Gately, J. Magram. 1997. Characterization of IL-12 receptor β1 chain (IL-12Rβ1)-deficient mice: IL-12Rβ1 is an essential component of the functional mouse IL- 12 receptor. J. Immunol. 159: 1658
Szabo, S. J., A. S. Dighe, U. Gubler, K. M. Murphy. 1997. Regulation of the interleukin (IL)-12Rβ2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J. Exp. Med. 185: 817
Gately, M. K., L. M. Renzetti, J. Magram, A. S. Stern, L. Adorini, U. Gubler, D. H. Presky. 1998. The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Annu. Rev. Immunol. 16: 495
Perussia, B., S. H. Chan, A. D'Andrea, K. Tsuji, D. Santoli, M. Pospisil, D. Young, S. F. Wolf, G. Trinchieri. 1992. Natural killer (NK) cell stimulatory factor or IL-12 has differential effects on the proliferation of TCR-α/β+, TCR-γ/δ lymphocytes, and NK cells. J. Immunol. 149: 3495
Chang, C. M., A. Limanni, W. H. Baker, M. E. Dobson, J. F. Kalinich, M. L. Patchen. 1997. Sublethal γ irradiation increases IL-1α, IL-6, and TNF-α mRNA levels in murine hematopoietic tissues. J. Interferon Cytokine Res. 17: 567
Oppmann, B., R. Lesley, B. Blom, J. C. Timans, Y. Xu, B. Hunte, F. Vega, N. Yu, J. Wang, K. Singh, et al 2000. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13: 715
Lenardo, M., K. M. Chan, F. Hornung, H. McFarland, R. Siegel, J. Wang, L. Zheng. 1999. Mature T lymphocyte apoptosis: immune regulation in a dynamic and unpredictable antigenic environment. Annu. Rev. Immunol. 17: 221
Parijs, L. V., A. K. Abbas. 1998. Homeostasis and self-tolerance in the immune system: turning lymphocytes off. Science 280: 243
Surh, C. D., J. Sprent. 2000. Homeostatic T cell proliferation: how far can T cells be activated to self-ligands?. J. Exp. Med. 192,4: F9
Janeway, C. A., Jr, P. Travers. 1999. Immunobiology, 4th Ed Garland Publishing, London.
Ku, C. C., M. Murakami, A. Sakamoto, J. Kappler, P. Marrack. 2000. Control of homeostasis of CD8+ memory T cells by opposing cytokines. Science 288: 675
Boursalian, T. E., K. Bottomly. 1999. Survival of naive CD4 T cells: roles of restricting versus selecting MHC class II and cytokine milieu. J. Immunol. 162: 3795
Boise, L. H., A. J. Minn, C. H. June, T. Lindsten, C. B. Thompson. 1995. Growth factors can enhance lymphocyte survival without committing the cell to undergo cell division. Proc. Natl. Acad. Sci. USA 92: 5491
Vella, A., T. K. Teague, J. Ihle, J. Kappler, P. Marrack. 1997. Interleukin 4 (IL-4) or IL-7 prevents the death of resting T cells: stat6 is probably not required for the effect of IL-4. J. Exp. Med. 186: 325
Kos, F. J., A. Mullbacher. 1993. IL-2-independent activity of IL-7 in the generation of secondary antigen-specific cytotoxic T cell responses in vitro. J. Immunol. 150: 387
Lynch, D. H., R. E. Miller. 1994. Interleukin 7 promotes long-term in vitro growth of antitumor cytotoxic T lymphocytes with immunotherapeutic efficacy in vivo. J. Exp. Med. 179: 31
Van Parijs, L., Y. Refaeli, J. D. Lord, B. H. Nelson, A. K. Abbas, D. Baltimore. 1999. Uncoupling IL-2 signals that regulate T cell proliferation, survival, and Fas-mediated activation-induced cell death. Immunity 11: 281
Willerford, D. M., J. Chen, J. A. Ferry, L. Davidson, A. Ma, F. W. Alt. 1995. Interleukin-2 receptor α chain regulates the size and content of the peripheral lymphoid compartment. Immunity 3: 521
Refaeli, Y., L. V. Parijs, C. A. London, J. Tschopp, A. K. Abbas. 1998. Biochemical mechanisms of IL-2-regulated Fas-mediated T cell apoptosis. Immunity 8: 615
Suzuki, H., T. M. Kundig, C. Furlonger, A. Wakeham, E. Timms, T. Matsuyama, R. Schmits, J. J. L. Simard, P. S. Ohashi, H. Griesser, et al 1995. Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor beta. Science 268: 1472
Gorelik, L., R. A. Flavell. 2000. Abrogation of TGFβ signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity 12: 171
Lucas, P. J., S. J. Kim, S. J. Melby, R. E. Gress. 2000. Disruption of T cell homeostasis in mice expressing a T cell-specific dominant negative transforming growth factor βII receptor. J. Exp. Med. 191: 1187
Letterio, J. J., A. B. Roberts. 1998. Regulation of immune responses by TGF-β. Annu. Rev. Immunol. 16: 137
Schmitt, E., P. Hoehn, C. Huels, S. Goedert, N. Palm, E. Rude, T. Germann. 1994. T helper type 1 development of naive CD4+ T cells requires the coordinate action of interleukin-12 and interferon-γ and is inhibited by transforming growth factor-β. Eur. J. Immunol. 24,4: 793
Ludviksson, B. R., D. Seegers, A. S. Resnick, W. Strober. 2000. The effect of TGF-β1 on immune responses of naive versus memory CD4+ Th1/Th2 T cells. Eur. J. Immunol. 30: 2101
Xu, H., G. X. Zhang, M. Wysocka, C. Y. Wu, G. Trinchieri, A. Rostami. 2000. The suppressive effect of TGF-β on IL-12-mediated immune modulation specific to a peptide Ac1–11 of myelin basic protein (MBP): a mechanism involved in inhibition of both IL-12 receptor β1 and β2. J. Neuroimmunol. 108: 53
Matzinger, P.. 1994. Tolerance, danger, and the extended family. Annu. Rev. Immunol. 12: 991
Janeway, C. A., Jr. 1989. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb. Symp. Quant. Biol. 54: 1
Shevach, E. M., J. T. Chang, B. M. Segal. 1999. The critical role of IL-12 and the IL-12Rβ2 subunit in the generation of pathogenic autoreactive Th1 cells. Springer Semin. Immunopathol. 21: 249
Falcone, M., N. Sarvetnick. 1999. Cytokines that regulate autoimmune responses. Curr. Opin. Immunol. 11: 670
Trinchieri, G.. 1998. Interleukin-12: a cytokine at the interface of inflammation and immunity. Adv. Immunol. 70: 83
Lo, D., C. Reilly, L. A. Marconi, L. Ogata, Q. Wei, G. Prud'homme, D. Kono, L. Burkly. 1995. Regulation of CD4 T cell reactivity to self and non-self. Int. Rev. Immunol. 13,2: 147
Gleeson, P. A., B. H. Toh, I. R. van Driel. 1996. Organ-specific autoimmunity induced by lymphopenia. Immunol. Rev. 149: 97
Modigliani, Y., A. Bandeira, A. Coutinho. 1996. A model for developmentally acquired thymus-dependent tolerance to central and peripheral antigens. Immunol. Rev. 149: 155
Bonomo, A., P. J. Kehn, E. M. Shevach. 1995. Post-thymectomy autoimmunity: abnormal T-cell homeostasis. Immunol. Today 16: 61
Annacker, O., O. Burlen-Defranoux, R. Pimenta-Araujo, A. Cumano, A. Bandeira. 2000. Regulatory CD4 T cells control the size of the peripheral activated/memory CD4 T cell compartment. J. Immunol. 164: 3573
You are going to email the following IL-12 Enhances CD8 T Cell Homeostatic Expansion
William C. Kieper, Martin Prlic, Clint S. Schmidt, Matthew F. Mescher, Stephen C. Jameson
The Journal of Immunology May 1, 2001, 166 (9) 5515-5521; DOI: 10.4049/jimmunol.166.9.5515
Innate Immunity Together with Duration of Antigen Persistence Regulate Effector T Cell Induction
Regulatory Roles of IL-2 and IL-4 in H4/Inducible Costimulator Expression on Activated CD4+ T Cells During Th Cell Development
Induction of CD4+ T Cell Apoptosis as a Consequence of Impaired Cytoskeletal Rearrangement in UVB-Irradiated Dendritic Cells
Show more CELLULAR IMMUNOLOGY AND IMMUNE REGULATION


Increasing knowledge about the role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology has led to the development of antibodies against this peptide or its receptor. However, CGRP is widely expressed throughout the body, participating not only in pathophysiological conditions but also in several physiological processes and homeostatic responses during pathophysiological events. Therefore, in this chapter, the risks of long-term blockade of the CGRP pathway will be discussed, with focus on the cardiovascular system, as this peptide has been described to have a protective role during ischemic events, and migraine patients present a higher risk of stroke and myocardial infarction.


text:
Democracy FCU Welcomes New CEO
Democracy Federal Credit Union Welcomes New President/CEO, Mr. Ken Cahoon
With the beginning of a New Year comes the welcoming of a new president and chief executive officer for Democracy Federal Credit Union. On January 2, Democracy FCU welcomed Ken Cahoon, who will succeed Kathy Geary as the president and CEO. Ms. Geary announced her retirement in the fall of 2018, after 37 years in the industry. Mr. Cahoon has more than 23 years of experience in the financial services industry and previously held the position of Vice President of Retail Delivery with the National Institute of Health Federal Credit Union.
"The Democracy FCU board of directors are honored to have Mr. Cahoon join the credit union in the distinguished role as president and CEO," said Patricia Ellis, Chairman. "His financial services background coupled with his years of experience in management, lending, and operations, make him an excellent choice for this position."
In his new role, Mr. Cahoon will ensure financial stability in the best interest of the members, the employees and the credit union while maintaining all aspects of the credit union's operations and activities in accordance with policies and procedures established by the board of directors. Mr. Cahoon will provide strategic direction, vision, and leadership to ensure that Democracy FCU's goals and objectives are being met.
Mr. Cahoon has accomplished a number of achievements in previous positions, where he began his career focusing on consumer and mortgage lending, branch operations, and quickly climbed the ladder to roles in management. Democracy FCU is looking forward to having him build on the successes of the credit union, and take it to the next level of excellence.
Mr. Cahoon is a graduate of California University of Pennsylvania where he earned a Bachelor of Science degree in Finance.


TierPoint, a US based IT company has announced plans to build a new data center in Allen, Texas. The initial phase of this facility will include an investment of over $20 million and 16,000 sq.ft. of raised floor.
The work on this data center is set to start immediately and the company expects the facility to be operational by next spring. TierPoint has teamed up with Compass Data Centers to construct the building which is designed to eventually grow to 90,000 sq.ft. and is located alongside an existing Cisco facility.
We see companies moving northward in the Dallas markets, organizations want to be close to their data.
That's why we made the decision to build the next facility up in Allen.
The new facility will be TierPoint's 40th data center across 18 American states. Parsons also mentioned that the company already has one Dallas facility in Irving Boulevard.
Our data center is filling up here in Dallas. We are seeing more demand for service in this market.