Lymphocytes that become large as a result of antigen stimulation
In immunology, reactive lymphocytes, variant lymphocytes, atypical lymphocytes, Downey cells or Türk cells are cytotoxic (CD8+) lymphocytes that become large as a result of antigen stimulation. Typically, they can be more than 30 μm in diameter with varying size and shape.
Discovery.
Reactive lymphocytes were originally described by W. Türk in 1907 in the peripheral blood of patients with infectious mononucleosis. Later in 1923 the features of the reactive lymphocytes were characterized in greater detail by Hal Downey and C.A. McKinlay, who also discovered the association with EBV and CMV.
Morphology.
Downey and McKinlay first described the atypical lymphocytes seen in cases of infectious mononucleosis. They further categorized the atypical lymphocytes of different etiologies under three subtypes:
Downey type II cell is the most common type of reactive lymphocyte. In general, those cells may vary in morphologic detail as well as surface marker characteristics since this is the result of a polyclonal immune response to antigenic stimulation. All three types of Downey cells were observed along with some other variants such as larger cells with deeply convoluted nucleus, cells with crystalline rods and granules in the cytoplasm, flame cells, Mott cells, and some intermediate forms.
The common features of reactive lymphocytes: 
Molecular markers.
Atypical lymphocyte population often express features of activated CD8+ T cells, such as CD29, CD38, HLA-DR, CD45RO and CD95. Expression of CD25 was on the other hand decreased.
Expressed molecular markers may vary depending on many factors. For example, CD57 expression seems to be significantly decreased only in patients with EBV infections.
Function.
The atypical lymphocytes have been best studied from blood of patients with infectious mononucleosis. Early studies suspect that atypical lymphocytes could have both T or B cells features; now it is more suggested that reactive lymphocytes are activated T-lymphocytes produced in response to infected B-lymphocytes.
Reactive lymphocytes have been found to accumulate in areas of inflammation like the liver and pharynx of individuals with infectious mononucleosis and skin window preparations. In infectious mononucleosis, the atypical lymphocytes are one component of a normal immune system that helps to control potentially fatal Epstein-Barr virus-induced B-cell lymphoma in human.
Causes.
Reactive lymphocytes are usually associated with viral illnesses, but they can also be present as a result of drug reactions (such as phenytoin), immunizations, radiation, and hormonal causes (such as stress and Addison's disease), as well as some autoimmune disorders (such as rheumatoid arthritis).
Some pathogen-related causes include:
Association with COVID-19.
The presence of Downey cells were observed in many COVID-19 cases, together with the atypical plasmacytoid lymphocytes (which could be one of the less usual atypical lymphocyte types).
Some observations even suggest that the presence of particular reactive lymphocytes in some of the infected patients could be an indicator of a better prognosis of the disease.