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.

Journal article

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.

Authors: Cobbold, S; Martin, G; Waldmann, H

• Publication status: Published
• Journal: European journal of immunology
• Volume: 20
• Issue: 12
• Pages: 2747-2755
• Publication date: 1990-12-01
• DOI: 10.1002/eji.1830201232
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Animals; Skin Transplantation; Immune Tolerance; Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; T-Lymphocytes; Antigens, CD4; Mice; Graft Survival; Major Histocompatibility Complex; Minor Histocompatibility Loci; Antigens, Surface; Mice, Inbred Strains; Antigens, Thy-1; Antigens, CD8; Histocompatibility