Studies on induction and control of cell-mediated autoimmunity. II. Prevention of induction and activity of autoreactive T cells by suppressor cells and by a suppressive serum factor.

Autoreactive T lymphocytes (T-ARC) can be detected in the spleen of mice treated with a single dose of cyclophosphamide (CY) (125 mg/kg), a peak occurring 6 days after CY injection. Eight days after CY treatment, the mice develop a specific anergic state. This anergic state can be transferred to normal syngeneic animals by either splenic nylon wool-nonadherent lymphocytes (suppressor cells, S-ARC) or by the serum of anergic mice, implying the development of an active suppressive mechanism due to CY treatment. Precursors of both potentially T-ARC as well as S-ARC coexist in the spleen of normal animals. Precursors of S-ARC present in the spleen and in the thymus of normal animals are sensitive to CY. However, committed S-ARC obtained from anergic mice are resistant to CY. Committed S-ARC as well as their precursors prevent induction of T-ARC. Committed S-ARC counteract expression of committed T-ARC activity, whereas precursors of S-ARC fail to do so. The autoimmune phenomenon described here represents an in vivo animal model system for induction of T-ARC and for the control mechanism which normally prevents induction and/or expression of cell-mediated autoreactivity by specific suppressor cells and by suppressive factors.