Natural CD4+ CD25+ regulatory T cells. Their role in the control of superantigen responses

CD4 regulatory T cells have a major role in controlling the immune response to self and foreign antigens. Natural CD4+ CD25+ T cells are a major component of the regulatory subset. Their absence is associated with the development of autoimmune and inflammatory diseases and with abnormal peripheral T-cell homeostasis. Two main characteristics discriminate natural CD4+ CD25+ T cells from their CD4+ CD25- counterparts, namely their cytokine production profile and their behavior during tolerance induction. Natural CD4+ CD25+ T cells produce interleukin (IL)-10, a cytokine that contributes to their regulatory role. They do not produce IL-2 and are dependent on exogenous IL-2 for proliferation in vitro and in vivo. Studies of their response to superantigen administration in vivo show that they are resistant to clonal deletion but can be tolerized by anergy. Their resistance to apoptosis may contribute to their continuous regulatory function, as it allows them to maintain permanent control over effector T cells.