LONG-TERM ACCEPTANCE OF PRIMARILY VASCULARIZED RENAL-ALLOGRAFTS IN MINIATURE SWINE - SYSTEMIC TOLERANCE VERSUS GRAFT ADAPTATION

We have previously demonstrated that tolerance to two-haplotype class I-mismatched renal allografts can be induced uniformly by a short cour se of cyclosporine. We report here that following transplant nephrecto my, 8 such long-term acceptor animals all accepted a second renal tran splant MHC matched to the original donor without additional immunosupp ression. These results indicate that the mechanism of tolerance to pri marily vascularized renal allografts involves modification of the host 's immune system by the first transplant. To assess the possibility th at ''graft adaptation'' is also involved in the maintenance of toleran ce, we retransplanted class I-disparate kidneys from tolerant animals into naive recipients MHC matched to the original recipient. Three of 4 such transplants were rejected acutely, while one animal demonstrate d a markedly prolonged survival, but also eventually rejected. These r esults, therefore, demonstrate that: (1) graft adaptation is not requi red in order to maintain tolerance; (2) graft acceptance involves indu ction of systemic tolerance; and (3) graft adaptation may participate in kidney graft prolongation but is not sufficient to transfer toleran ce to a secondary host.