Converging experimental evidence indicates that the clinical expression of autoimmunity is under the control of T cell-mediated immunoregulatory circuits. Several types of suppressor T cells have been described. Some of them are closely dependent upon cytokines such as TH2 cells and Tr1 cells. Others appear to rely more on cell-cell contact (such as CD25+ CD62L+ T cells), although some cytokines, notably TGF-beta, may be involved in their growth or their mode of action. It is tempting to separate suppressor cells that appear spontaneously, such as CD25+ T cells and NKT cells (innate immunoregulation), from those that are only observed after antigen administration, such as TH2 cells and Tr1 cells (adaptive immunoregulation). The role of these diverse cell types in the control of the onset or the progression of autoimmune diseases is likely, but still a matter of debate. A central question is to determine whether immune dysregulation precedes the burst of pathogenic autoimmunity.