The induction of skin graft tolerance in major histocompatibility complex-mismatched or primed recipients: primed T cells can be tolerized in the periphery with anti-CD4 and anti-CD8 antibodies

Eur J Immunol. 1990 Dec;20(12):2747-55. doi: 10.1002/eji.1830201232.

Abstract

Mice given short courses of anti-CD4 and anti-CD8 monoclonal antibodies became tolerant of allogeneic skin grafted at the same time. Tolerance could be obtained without T cell depletion across multiple minor antigen mismatches, both in naive and primed animals, demonstrating that peripheral T cells could be tolerized, even if they had been previously activated. Where donor and recipient were incompatible across the whole major histocompatibility complex, specific tolerance could be achieved by using a combination of depleting followed by non-depleting antibodies, where each alone was unsuccessful. Although mice clearly tolerated their original skin grafts, we observed in some strain combinations that a second fresh, but genotypically identical graft, was slowly rejected. Such mice also possessed T cells which could proliferate to donor-type stimulator cells in vitro. Whatever the mechanisms, we have demonstrated that operational transplantation tolerance can be achieved with simple, non-toxic antibody therapy. The introduction of comparable tolerance-inducing regimens in clinical organ transplantation could obviate the need for long-term immunosuppression and its unfortunate side effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Antigens, Surface / immunology
  • CD4 Antigens / immunology*
  • CD8 Antigens
  • Graft Survival
  • Histocompatibility
  • Immune Tolerance*
  • Major Histocompatibility Complex*
  • Mice
  • Mice, Inbred Strains
  • Minor Histocompatibility Loci
  • Skin Transplantation / immunology*
  • T-Lymphocytes / immunology*
  • Thy-1 Antigens

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Surface
  • CD4 Antigens
  • CD8 Antigens
  • Thy-1 Antigens