CTLA-4 expression on antigen-specific cells but not IL-10 secretion is required for oral tolerance.
CD4(+) T cells play a vital role in mediating the tolerance induced at mucosal sites following exposure to non-pathogenic stimuli, and further understanding of the precise mechanisms by which these cells prevent aberrant responses is required. We have developed a model using transfer of DO11.10 TCR-...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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2002
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| _version_ | 1797099512247877632 |
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| author | Fowler, S Powrie, F |
| author_facet | Fowler, S Powrie, F |
| author_sort | Fowler, S |
| collection | OXFORD |
| description | CD4(+) T cells play a vital role in mediating the tolerance induced at mucosal sites following exposure to non-pathogenic stimuli, and further understanding of the precise mechanisms by which these cells prevent aberrant responses is required. We have developed a model using transfer of DO11.10 TCR-transgenic bone marrow into irradiated recipients in which it has been possible to track antigen-specific CD4(+) cells in mesenteric lymph nodes (mLN), Peyer's patches (PP) and lamina propria following primary exposure to antigen. Using this model we have demonstrated initial activation in all three gut-associated lymphoid tissue compartments characterized by increases in the frequency of transgenic cells expressing CD69 and CD25. These cells subsequently enter a state of hyporesponsiveness both locally in the mLN and PP and in the periphery following feeding and challenge. Investigating the role of CTLA-4 either using anti-CTLA-4 mAb or by generating chimeras using DO11.10xCTLA-4(-/-) mice as donors we have clearly shown that antigen-specific cells require the expression of this regulatory molecule for oral tolerance. In contrast, oral tolerance was intact in chimeras generated using DO11.10xIL-10(-/-) cells, indicating that secretion of this cytokine by antigen-specific cells is not required. |
| first_indexed | 2024-03-07T05:24:48Z |
| format | Journal article |
| id | oxford-uuid:e030ce7a-6fc9-4b79-895e-4622d6057276 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:24:48Z |
| publishDate | 2002 |
| record_format | dspace |
| spelling | oxford-uuid:e030ce7a-6fc9-4b79-895e-4622d60572762022-03-27T09:45:07ZCTLA-4 expression on antigen-specific cells but not IL-10 secretion is required for oral tolerance.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e030ce7a-6fc9-4b79-895e-4622d6057276EnglishSymplectic Elements at Oxford2002Fowler, SPowrie, FCD4(+) T cells play a vital role in mediating the tolerance induced at mucosal sites following exposure to non-pathogenic stimuli, and further understanding of the precise mechanisms by which these cells prevent aberrant responses is required. We have developed a model using transfer of DO11.10 TCR-transgenic bone marrow into irradiated recipients in which it has been possible to track antigen-specific CD4(+) cells in mesenteric lymph nodes (mLN), Peyer's patches (PP) and lamina propria following primary exposure to antigen. Using this model we have demonstrated initial activation in all three gut-associated lymphoid tissue compartments characterized by increases in the frequency of transgenic cells expressing CD69 and CD25. These cells subsequently enter a state of hyporesponsiveness both locally in the mLN and PP and in the periphery following feeding and challenge. Investigating the role of CTLA-4 either using anti-CTLA-4 mAb or by generating chimeras using DO11.10xCTLA-4(-/-) mice as donors we have clearly shown that antigen-specific cells require the expression of this regulatory molecule for oral tolerance. In contrast, oral tolerance was intact in chimeras generated using DO11.10xIL-10(-/-) cells, indicating that secretion of this cytokine by antigen-specific cells is not required. |
| spellingShingle | Fowler, S Powrie, F CTLA-4 expression on antigen-specific cells but not IL-10 secretion is required for oral tolerance. |
| title | CTLA-4 expression on antigen-specific cells but not IL-10 secretion is required for oral tolerance. |
| title_full | CTLA-4 expression on antigen-specific cells but not IL-10 secretion is required for oral tolerance. |
| title_fullStr | CTLA-4 expression on antigen-specific cells but not IL-10 secretion is required for oral tolerance. |
| title_full_unstemmed | CTLA-4 expression on antigen-specific cells but not IL-10 secretion is required for oral tolerance. |
| title_short | CTLA-4 expression on antigen-specific cells but not IL-10 secretion is required for oral tolerance. |
| title_sort | ctla 4 expression on antigen specific cells but not il 10 secretion is required for oral tolerance |
| work_keys_str_mv | AT fowlers ctla4expressiononantigenspecificcellsbutnotil10secretionisrequiredfororaltolerance AT powrief ctla4expressiononantigenspecificcellsbutnotil10secretionisrequiredfororaltolerance |