during a tolerant state potential effector cells remain but are tightly regulated by induced antigen-specific cd4+ regulatory t cells (itregs). many subsets of itregs play a part in this proces, but cd4cd25foxp3 tregs play a key role, because they have the ability to convert conventional t cells into itregs directly by secretion of the suppressive cytokines tgf-β, il-10 or il-35, or indirectly via dendritic cells (dcs). production of il-10 induces the formation of another population of regulatory t cells called tr1. tr1 cells are dependent on il-10 and tgf-β as well as tregs, but differ from them by lacking expression of foxp3. high il-10 production is characteristic for tr1 cells themselves and they also produce tgf-β. in the presence of il-10 can be also induced tolerogenic dcs from monocytes, whose production of il-10 is also important for tr1 formation. these interactions lead to the production of enzymes such as ido (indolamine 2,3-dioxygenase) that catabolize essential amino acids. this microenvironment with a lack of essential amino acids together with other signals results in mtor (mammalian target of rapamycin) inhibition which, particularly in synergy with tgf-β, direct the induction of new foxp3 (forkhead box protein 3) expressing tregs.