Differential Effects of X-Irradiation and Cyclosporin-A Administration on the Thymus with Respect to the Generation of Cyclosporin-A-Induced Autoimmunity

Cyclosporin A (CsA), a potent inhibitor of T-cell activation, has been shown to have several effects on thymocyte maturation, thymic stromal cells, and the generation of autoreactive T cells. In Lewis rats, the combination of lethal irradiation, syngeneic bone marrow transplantation, and a 4-week course of CsA administration causes the development of an autoimmune disease (CsA-AI) resembling allogeneic graft-versus-host disease. This occurs upon withdrawal of CsA, provided the thymus receives irradiation and is present during CsA treatment. In this study, the separate effects of irradiation or CsA treatment on thymic stromal cells and thymocytes, compared to the combinatory effects, were examined using immunohistochemistry and tricolor flow cytometric analysis