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
| Autor: | Stephen P. Cobbold, Gilly Martin, Herman Waldmann |
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| Rok vydání: | 1990 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte Minor Histocompatibility Loci medicine.drug_class CD8 Antigens T-Lymphocytes Immunology Mice Inbred Strains Major histocompatibility complex Monoclonal antibody Immune tolerance Major Histocompatibility Complex Mice Antigen medicine Immune Tolerance Immunology and Allergy Animals biology Graft Survival Antibodies Monoclonal T lymphocyte Skin Transplantation Histocompatibility Transplantation Antigens Surface CD4 Antigens biology.protein Thy-1 Antigens CD8 |
| Zdroj: | European journal of immunology. 20(12) |
| ISSN: | 0014-2980 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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