CELL-MEDIATED AUTOIMMUNE RESPONSE TO TESTIS INDUCED BY BILATERAL TESTICULAR INJURY CAN BE SUPPRESSED BY CYCLOSPORIN A

Abstract

Purpose Since the delayed type hypersensitivity (DTH) response to testis antigens plays a key role in the induction and/or maintenance of experimental autoimmune orchitis (EAO), an animal model for human immunological male infertility or aspermatogenesis, we have investigated the immunosuppressive effect of cyclosporin A (CsA) on the DTH response to autologous testicular cells (TC). Materials and Methods A DTH response to autologous TC was induced in C3H/HeN mice by bilateral testicular injury (trauma). CsA was administered intraperitoneally for 10 consecutive days before and after injury. A DTH response was assessed by measuring delayed footpad reaction (DFR) to autologous TC 9 days after injury. Results When the mice were traumatized alone, 10 mg./kg. or more of CsA suppressed the DTH response to autologous TC significantly. In mice traumatized with 100 mg./kg. of cyclosphosphamide (CY)-pretreatment, 30 mg./kg. or more of CsA was needed to suppress the DTH response. In mice traumatized with 200 mg./kg. of CY-pretreatment, 50 mg./kg. of CsA was needed to suppress the autoimmune response. Conclusions The DTH response to autologous TC was suppressed significantly by administration of CsA in a dose-dependent manner. We have also shown the direct suppressive effect of CsA on effector cells for DTH by means of local passive transfer of DTH. Administration of CsA had no augmenting or suppressive effect on suppressor cells for DTH. CsA might be a significant drug for the immunosuppression of EAO and possibly for immunological male infertility.