Cumulative evidence has shown that extrathymic T cells can be autoreactive and that B-1 cells may produce autoantibodies. These T and B-1 cells, which form part of the innate immune system, tend to be activated simultaneously when conventional T and B cells are in a suppressive state, for example, when thymic atrophy occurs by stress or involution with aging. In other words, autoreactive T cells and autoantibody-producing B cells are different from thymus-derived T cells and bone marrow-derived B cells. Activated extrathymic T cells and B-1 cells are often observed in numerous autoimmune diseases, aging, malarial infection and chronic graft-versus-host disease. It is thought that the autoreactivity of extrathymic T cells and B-1 cells may be important for the elimination of "abnormal self" tissues or cells. However, over-activation of innate lymphocytes may be related to the onset of disease or self-tissue destruction. However, it must be emphasized that the autoreactivity of innate lymphocytes is not generated by failure of the thymic pathway of T-cell differentiation or the conventional pathway of B-2 cells.