title: Tolerance to limb tissue allografts between swine matched for major histocompatibility complex antigens.
abstract: Transplantation of limb tissue allografts would greatly expand the realm of reconstructive surgery. However, the toxicity of chronic immunosuppression has adversely tilted the risk-benefit balance for clinical transplant. In this study, a procedure was sought to achieve host tolerance to limb tissue allografts through matching of the major histocompatibility complex (MHC) antigens between donor and host swine using only a 12-day course of cyclosporine. 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 histologic sections. Allografts from MHC-matched, minor antigen mismatched donors not treated with cyclosporine (n = 4) were rejected between 9 and 12 weeks. Allografts from similarly matched donors treated with 12 days of cyclosporine (n = 7) showed no evidence of rejection until sacrifice between 25 and 47 weeks. Thus allograft tolerance was achieved between MHC-matched swine using a limited course of cyclosporine. Demonstration of limb tissue allograft survival in a large animal model without long-term immunosuppression represents an important step toward clinical transplantation.
authors.affiliation: Plastic Surgery Research Laboratory and Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA. lee.wpa@mgh.harvard.edu
authors.forename: W P
authors.initials: WP
authors.lastname: Lee
authors.forename: J P
authors.initials: JP
authors.lastname: Rubin
authors.forename: J L
authors.initials: JL
authors.lastname: Bourget
authors.forename: S R
authors.initials: SR
authors.lastname: Cober
authors.forename: M A
authors.initials: MA
authors.lastname: Randolph
authors.forename: G P
authors.initials: GP
authors.lastname: Nielsen
authors.forename: F L
authors.initials: FL
authors.lastname: Ierino
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008285:Major Histocompatibility Complex; D023421:Models, Animal; D013556:Swine, Miniature; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine