Induction of autoreactive T lymphocytes and their suppressor cells by cyclophosphamide

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THERE is increasing evidence of potentially autoreactive cells in normal animals1,2. Expression of autoimmunity, however, may not arise as a primary effector cell abnormality but more possibly as the consequence of a defect in a thymus-dependent control mechanism3–5. Cyclophosphamide (CY) enhances the capacity of mice to give T cell-dependent responses, such as delayed type hypersensitivity (DTH) induced by sheep red blood cells6. It was suggested that B cells were the targets of CY action7 and that the enhanced DTH reaction was due to inhibition of antibody production and consequently to lack of the antigen–antibody complexes responsible for inhibition of DTH. Askenase et al.8 presented evidence for an alternative explanation for enhancement of DTH by CY. They demonstrated augmented DTH to sheep red blood cells with doses of CY which did not influence antibody responses, suggesting the existence of CY-sensitive suppressor cells. Similar conclusions have been drawn by Roellinghoff et al.9, who observed induction of cytotoxic lymphocytes in mice to hapten-conjugated syngeneic cells after treatment with CY. We report here that injection of normal mice with CY results in manifestation of autoreactive T lymphocytes followed by the appearance of suppressor cells counteracting autoreactivity.