Tolerance to limb tissue allografts between swine matched for major histocompatibility complex antigens

Transplantation of limb tissue allografts would greatly expand the realm of reconstructive surgery. Ho it ever, the toxicity of chronic immunosuppress ion has adversely tilted the risk-benefit balance for clinical transplant. In this study, a procedure was sought to achieve host tolerance to limb tis sue allografts through matching of the major histocompatibility complex (MH C) antigens between donor and host swine using only a 12-day course of cycl osporine. Massachusetts General Hospital (MGH) miniature swine were used as a large animal model with defined MHC, and musculoskeletal grafts from the donor hind limb were transplanted heterotopically to the recipient femoral vessels. Allografts from MHC-mismatched donors treated with cyclosporine ( n = 4) were rejected in less than 6 weeks by gross inspection and histologi c sections. Allografts from MHC-matched, minor antigen mismatched donors no t treated with cyclosporine (n = 4) were rejected between 9 and 12 weeks. A llografts from similarly matched donors treated with 12 days of cyclosporin e (n = 7) showed no evidence of rejection until sacrifice between 25 and 47 weeks. Thus allograft tolerance was achieved between MHC-matched swine usi ng a limited course of cyclosporine. Demonstration of limb tissue anograft survival in a large animal model without long-term immunosuppression repres ents an important step toward clinical transplantation.