Cyclosporine-induced specific unresponsiveness to retinal soluble antigen in experimental autoimmune uveoretinitis

Cyclosporine (CsA) was previously reported to effectively suppress the induction of experimental autoimmune uveoretinitis (EAU) in rats immunized with S-antigen. The present study provides information concerning the development of specific unresponsiveness in the CsA-treated rats. The majority of Lewis rats immunized with S-antigen and treated with CsA from Day 0 to Day 14 failed to develop EAU when reimmunized with S-antigen on Day 30. In contrast, similarly treated rats were fully susceptible to induction of experimental allergic encephalomyelitis when immunized with myelin basic protein, or even to EAU when immunized with another retinal antigen, interphotoreceptor retinoid-binding protein (IRBP). The possible involvement of suppressor cells in establishing the unresponsiveness state was indicated by experiments both in vitro and in vivo. The enriched fractions of suppressor cells from rats unresponsive to induction of EAU by S-antigen were found to inhibit the specific mitotic response of lymphocytes to S-antigen, but had no effect on the response to IRBP. In vivo, injection of such enriched suppressor cell fractions to naive syngenic rats inhibited or delayed the development of EAU following immunization with S-antigen. It is proposed, therefore, that specific unresponsiveness plays a role in the suppression of EAU by CsA and that the unresponsiveness is mediated in part by specific suppressor cells.