Tolerance and suppression in a primed immune system.
The induction of tolerance in a primed immune system would be valuable therapeutically, but has been difficult to achieve. Mice primed to multiple minor histoincompatible antigens (minors) are able to rapidly reject secondary grafts using either their CD4+ or CD8+ T-cell subpopulations. Short course...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1996
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| _version_ | 1797069446848708608 |
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| author | Marshall, SE Cobbold, S Davies, J Martin, G Phillips, J Waldmann, H |
| author_facet | Marshall, SE Cobbold, S Davies, J Martin, G Phillips, J Waldmann, H |
| author_sort | Marshall, SE |
| collection | OXFORD |
| description | The induction of tolerance in a primed immune system would be valuable therapeutically, but has been difficult to achieve. Mice primed to multiple minor histoincompatible antigens (minors) are able to rapidly reject secondary grafts using either their CD4+ or CD8+ T-cell subpopulations. Short courses of treatment with nonlytic anti-CD4 and anti-CD8 antibodies targeted at both T-cell subsets can induce long-term peripheral T-cell tolerance in primed mice. We examine the mechanisms by which peripheral tolerance is maintained, and show that tolerant mice harbor CD4+ T cells capable of specifically suppressing rejection mediated by either subset of primed T cells. Remarkably, elimination of CD4+ T cells from tolerant mice resulted in graft rejection, suggesting that graft-reactive CD8+ T cells had not been eliminated, but had been under continuous regulation by "tolerant" CD4+ T cells. This result demonstrates that it may be possible to establish therapeutic operational tolerance without permanently inactivating all antigen-reactive cells. |
| first_indexed | 2024-03-06T22:24:35Z |
| format | Journal article |
| id | oxford-uuid:563bfb1e-b720-44d6-a3fc-c7f8948f229b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:24:35Z |
| publishDate | 1996 |
| record_format | dspace |
| spelling | oxford-uuid:563bfb1e-b720-44d6-a3fc-c7f8948f229b2022-03-26T16:48:58ZTolerance and suppression in a primed immune system.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:563bfb1e-b720-44d6-a3fc-c7f8948f229bEnglishSymplectic Elements at Oxford1996Marshall, SECobbold, SDavies, JMartin, GPhillips, JWaldmann, HThe induction of tolerance in a primed immune system would be valuable therapeutically, but has been difficult to achieve. Mice primed to multiple minor histoincompatible antigens (minors) are able to rapidly reject secondary grafts using either their CD4+ or CD8+ T-cell subpopulations. Short courses of treatment with nonlytic anti-CD4 and anti-CD8 antibodies targeted at both T-cell subsets can induce long-term peripheral T-cell tolerance in primed mice. We examine the mechanisms by which peripheral tolerance is maintained, and show that tolerant mice harbor CD4+ T cells capable of specifically suppressing rejection mediated by either subset of primed T cells. Remarkably, elimination of CD4+ T cells from tolerant mice resulted in graft rejection, suggesting that graft-reactive CD8+ T cells had not been eliminated, but had been under continuous regulation by "tolerant" CD4+ T cells. This result demonstrates that it may be possible to establish therapeutic operational tolerance without permanently inactivating all antigen-reactive cells. |
| spellingShingle | Marshall, SE Cobbold, S Davies, J Martin, G Phillips, J Waldmann, H Tolerance and suppression in a primed immune system. |
| title | Tolerance and suppression in a primed immune system. |
| title_full | Tolerance and suppression in a primed immune system. |
| title_fullStr | Tolerance and suppression in a primed immune system. |
| title_full_unstemmed | Tolerance and suppression in a primed immune system. |
| title_short | Tolerance and suppression in a primed immune system. |
| title_sort | tolerance and suppression in a primed immune system |
| work_keys_str_mv | AT marshallse toleranceandsuppressioninaprimedimmunesystem AT cobbolds toleranceandsuppressioninaprimedimmunesystem AT daviesj toleranceandsuppressioninaprimedimmunesystem AT marting toleranceandsuppressioninaprimedimmunesystem AT phillipsj toleranceandsuppressioninaprimedimmunesystem AT waldmannh toleranceandsuppressioninaprimedimmunesystem |