Effect of cyclosporin A on T cell immunity. II. Defective thymic education of CD4 T helper cell function in cyclosporin A-treated mice.

Cyclosporin A (CsA) is an immunosuppressive agent that is widely used in transplantation. Recent animal studies indicate that CsA can affect the development of immunity so that autoreactive T lymphocytes are generated. In this study, mice were treated with CsA prior to irradiation and transplantation of syngeneic bone marrow to determine whether CsA pretreatment would affect the ability of the bone marrow recipients to develop normal T cell function. Our results indicate that (a) thymuses of CsA-treated mice do not contain single-positive thymocytes (i.e. L3T4+Ly-2- or L3T4-Ly-2+) during i.p. treatment with 15 mg/kg/day of CsA; (b) both populations of single-positive thymocytes reappear within 2 weeks of termination of CsA and (c) irradiation and bone marrow reconstitution of these CsA-treated mice results in reconstitution of normal numbers of L3T4+ and Ly-2+ cells, but the L3T4+ T cells to not provide T helper function, as determined by interleukin 2 production and cytotoxic T lymphocytes generation. These findings indicate that CsA can affect thymic microenvironment and may be important as a model for investigating intrathymic T cell maturation. Our results may also have clinical implications for T lymphocyte development in transplant patients receiving CsA.