Induction of fonor specific unresponsiveness by pre-operative administraton of donor antigen in combination with a short course of cyclosporine in rat allogeneic kidney transplantation.

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The immunosuppressive effect of the combination of a therr day coures of cyclosporine (CsA) with one i.v. injection of 3 mol KCL extracted donor antigen of donor blood transfusion was tested on rat allogeneic kidney transplantation. Administration of 10 mg/Kg/day CsA alone for three days slightly prolonged Buffalo (BUF) kidney allograft survival time from 7 to 11 days in Wistar-Furth (WF) rats. The combination of CsA with donor antigen or with donor blood transfusion administered one day prior to transplantation caused greater donor specific prolongation of graft survival. Lymphocytes harvested from recipient 10 days after transplantation that had received combined therapy with CaA and donor antigen not only displayed specific unrsponsiveness to donor stimulator cells in MLR but also specifically suppressed the proliferative response of vergin WF responder cell to donor BUF stimulator cells. Furthermore suppressor cell activeity was subbgested by diminished responses of local GVHR in popliteal lymph nodes of totally irraddiated BUF rats, but not in those of third party Brown Norway rats, and by prolongation of BUF kinney allograft survival following systemic adoptive transfer. Administeration of low dosw cyclophosphamide reduced the capacity to prolong graft survival. Two additionla cycles of CSA therapy at 10-day intervals administered in an attempt to maintain T suppressor dominance over T helper cell prolonged median graft survival to 65 days. Similar prolongation was not achieved using donor blood transfusion. These findings suggest that donor antigen amlifies the induction of specific suppressor cells and CsA facilitates the establishment of suppressor cell dominance, leading to host unresponsiveness.