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.
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...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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1990
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| _version_ | 1797064268106956800 |
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| author | Cobbold, S Martin, G Waldmann, H |
| author_facet | Cobbold, S Martin, G Waldmann, H |
| author_sort | Cobbold, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T21:11:49Z |
| format | Journal article |
| id | oxford-uuid:3e703f15-2bf1-4a3b-8786-ae8995dc0056 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:11:49Z |
| publishDate | 1990 |
| record_format | dspace |
| spelling | oxford-uuid:3e703f15-2bf1-4a3b-8786-ae8995dc00562022-03-26T14:25:31ZThe 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 articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3e703f15-2bf1-4a3b-8786-ae8995dc0056EnglishSymplectic Elements at Oxford1990Cobbold, SMartin, GWaldmann, HMice 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. |
| spellingShingle | Cobbold, S Martin, G Waldmann, H 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. |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
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