INDUCTION OF LONG-TERM GRAFT TOLERANCE AND DONOR-RECIPIENT CHIMERISM

We compared the effect of different immunosuppressive drug regimens on both mean and long-term allograft survival and the histologic appeara nce of donor/recipient chimeras in the ACI to Lewis rat heterotopic ca rdiac transplant model. Intraabdominal cardiac transplantation was per formed in standard fashion and microchimerism was assessed using immun ohistochemical staining of cut sections of recipient spleen and lymph nodes. All of the drug regimens studied resulted in excellent mean all ograft survival. Furthermore, long-term (>120 day) allograft survival was consistently observed in each group. In fact, many of the recipien ts continue to have functioning heterotopic grafts even as they approa ch the end of the natural life span of a Lewis rat. Mixed allogeneic c himerism, however, was not observed with 100% frequency despite the co nsistent induction of graft tolerance. This finding may be related to the immunosuppressive agents used or the sensitivity of the immunohist ochemical assay. Therefore, the exact role, if any, of chimerism in th e induction of graft tolerance remains unanswered. (C) 1996 Academic P ress, Inc.