RETRANSPLANTATION IN MINIATURE SWINE - LACK OF A REQUIREMENT FOR GRAFT ADAPTATION FOR MAINTENANCE OF SPECIFIC RENAL-ALLOGRAFT TOLERANCE

In miniature swine, one-haplotype class I disparate renal allografts a re accepted without exogenous immunosuppression by approximately 35% o f 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 cyclosporine. In vitro studies of recipient cell-mediated lymphocyt otoxicity responses have shown donor-specific cytotoxic T lymphocyte c lones in tolerant animals, suggesting that tolerance may be a local ph enomenon or a central phenomenon activated in the milieu of the graft. Six animals were retransplanted with kidneys MHC-matched to their ori ginal allograft to determine whether (1) tolerance is a central phenom enon; (2) host tolerance can be broken with a fresh challenge of donor antigen and antigen-presenting cells; and (3) graft adaptation is req uired for maintenance of tolerance. Four of the retransplanted animals had been spontaneous acceptors of one-haplotype class I-disparate gra fts and two had been rendered tolerant to two-haplotype class I-mismat ched kidneys with CsA induction. All six explanted allografts showed n o histological evidence of rejection and all six retransplants were ac cepted without exogenous immunosuppression. These findings suggest tha t in miniature swine tolerance of class I-disparate kidneys is a stabl e, centrally mediated phenomenon that cannot be broken with a challeng e of fresh donor antigen and donor-type APCs. Furthermore, successful retransplantation without immunosuppression in animals receiving CsA i nduction therapy for their first transplant suggests that graft adapta tion is not necessary for the maintenance of tolerance.