Background. The authors have examined the mechanism whereby co-transplantation of a kidney and heart from the same donor induces and maintains tolerance to both organs in miniature swine. Methods. Transplants were performed across a major histocompatibility complex class I mismatch, and recipients received cyclosporine for 12 days. Group 1 animals received heart transplants alone (n = 5), and all other groups received both heart and kidney allografts. Group 2 animals received no further intervention (n = 2). Group 3 animals underwent transplant nephrectomy 8 days after heart and kidney co-transplantation (n = 2). Group 4 animals underwent transplant nephrectomy 100 days after co-transplantation (n = 2). Skin grafts were placed on group 4 animals, on one group 3 animal, and on two animals from group 2. Group 5 animals underwent thymectomy 100 days after co-transplantation (n = 4). Results. Group 1 animals developed cardiac allograft vasculopathy (CAV) and rejection. Group 2 animals never developed CAV and demonstrated in vitro donor-specific unresponsiveness. Group 3 animals suffered CAV and rejection. Group 4 animals developed CAV without concomitant donor-specific cell-mediated lympholysis reactivity, interstitial rejection, or cessation of graft function. Skin grafts on group 3 and group 4 animals led to fulminant rejection of heart and skin grafts, in contrast to grafts on group 2 animals that had no in vivo effect. Group 5 animals developed CAV but no significant increase in interstitial infiltrates. Conclusions. Both the kidney and thymus were necessary for maintenance of tolerance to heart allografts.
- Cytotoxic T lymphocyte
- Major histocompatibility complex
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