Accumulating evidence indicates that T cell-mediated dominant control of self-reactive T cells contributes to the maintenance of immunologic self-tolerance and its alternation may lead to development of autoimmune disease. Efforts to delineate such a regulatory T cell population have revealed that CD25+ cells within the CD4+ population in normal naive animals including humans possess the regulatory activity. The CD25+CD4+ regulatory T cells are produced by the normal thymus as a functionally distinct subpopulation of T cells. They play critical roles not only in preventing autoimmunity but also in controlling various immune reactions.