Retransplantation in miniature swine: Lack of a requirement for graft adaptation for maintenance of specific renal allograft tolerance

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Journal Article

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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 cyclosporine. In vitro studies of recipient cell-mediated lymphocytotoxicity responses have shown donor-specific cytotoxic T lymphocyte clones in tolerant animals, suggesting that tolerance may be a local phenomenon or a central phenomenon activated in the milieu of the graft. Six animals were retransplanted with kidneys MHC-matched to their original allograft to determine whether (1) tolerance is a central phenomenon; (2) host tolerance can be broken with a fresh challenge of donor antigen and antigen-presenting cells; and (3) graft adaptation is required for maintenance of tolerance. Four of the retransplanted animals had been spontaneous acceptors of one-haplotype class I-disparate grafts and two had been rendered tolerant to two-haplotype class I-mismatched kidneys with CsA induction. All six explanted allografts showed no histological evidence of rejection and all six retrans-plants were accepted without exogenous immunosuppression. These findings suggest that in miniature swine tolerance of class I-disparate kidneys is a stable, centrally mediated phenomenon that cannot be broken with a challenge of fresh donor antigen and donor-type APCs. Furthermore, successful retrans-plantation without immunosuppression in animals receiving CsA induction therapy for their first transplant suggests that graft adaptation is not necessary for the maintenance of tolerance. © 1994 by Williams and Wilkins.

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