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

Plast Reconstr Surg. 2001 May;107(6):1482-90; discussion 1491-2. doi: 10.1097/00006534-200105000-00027.

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.

MeSH terms

  • Animals
  • Cyclosporine / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Major Histocompatibility Complex
  • Models, Animal*
  • Swine, Miniature
  • Transplantation Immunology*
  • Transplantation, Homologous

Substances

  • Immunosuppressive Agents
  • Cyclosporine