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Previous studies in miniature swine have suggested that the mechanism underlying the spontaneous development of tolerance in one third of one-haplotype class I disparate renal allografts (i.e., ag----ad) involves a relative T cell help deficit at the time of first exposure to antigen. If this hypothesis were correct, then one might expect the administration(More)
We have previously demonstrated that a 12-day course of cyclosporine A (CsA) leads to the induction of tolerance to renal allografts in 100% of recipients selectively mismatched at class I for both haplotypes, and in 71% of recipients selectively mismatched at class II for both haplotypes, but in 0% of recipients mismatched for two haplotypes at both class(More)
Major histocompatibility complex class II matching is of overwhelming importance for achieving tolerance to kidney transplants (KTX) in miniature swine. When class II antigens are matched, long-term specific tolerance across complete MHC class I antigen barriers can uniformly be induced by a 12-day perioperative course of cyclosporine. This same regimen is(More)
BACKGROUND Recent studies in young (5-7 months) miniature swine have demonstrated that the thymus is involved in the rapid induction of stable tolerance to class I mismatched renal allografts after a 12-day course of Cyclosporine (CyA). Because both steroids and age are known to influence the structure and function of the thymus, we have now studied the(More)
Miniature swine that become tolerant to renal allografts across an MHC class I barrier following a short course of cyclosporine are unresponsive to donor class I antigens in cell-mediated lymphocytotoxicity. However, skin grafts bearing donor class I plus third-party class II antigens are promptly rejected, and the animals then develop marked cell-mediated(More)
We have previously demonstrated that tolerance to two-haplotype class I-mismatched renal allografts can be induced uniformly by a short course of cyclosporine. We report here that following transplant nephrectomy, 8 such long-term acceptor animals all accepted a second renal transplant MHC matched to the original donor without additional immunosuppression.(More)
Previous work from this laboratory demonstrated that tolerance to MHC-identical or class I-disparate renal allografts develops in approximately one third of miniature swine without exogenous immunosuppression. A back-cross study indicated that rejection of MHC-identical transplants due to minor Ag was controlled by one or possibly two non-MHC-linked,(More)
Our laboratory has reported previously spontaneous acceptance of class II-matched, single haplotype (but not 2 haplotype), class I-mismatched renal allografts in miniature swine. All class II-mismatched animals rejected acutely regardless of class I matching. We have also demonstrated recently that a short course of high dose (10 mg/kg/day for 12 days) CsA(More)
In miniature swine, one-haplotype class I disparate renal allografts are accepted without exogenous immunosuppression by approximately 35% of recipients. Alternatively, transplants bearing a two-haplotype class I mismatch are always rejected acutely. However, long-term acceptance in the latter animals can be achieved uniformly with a 12-day course of(More)