Studies on induction and control of cell-mediated autoimmunity. I. Induction of "autoreactive" T lymphocytes in mice by cyclophosphamide.

Injection of a single dose of cyclophosphamide (CY) (125 mg/kg) or a combination of a small dose of CY (20 mg/kg) and 2.5 mg/kg lipopolysaccharide induces a transient appearance of autoreactive T lymphocytes (T-ARC) in the spleens of mice. The T-ARC activity reaches a peak 6 days after CY injection and could not be detected 8 days after this treatment. For testing T-ARC activity, spleen cells were injected into the footpads of syngeneic recipients, and the resulting lymph node enlargement at the draining site of cell inoculation and the content of nucleated cells in the lymph node was determined. Possible explanations of this autoimmune phenomenon are discussed. It is postulated that CY-resistant precursors of T-ARC are stimulated by "new" antigenic sites present on the surface of B lymphoblasts repopulating the CY-damaged spleen in a period of transient absence of CY-sensitive suppressor cells.