Generation of anergic and regulatory T cells following prolonged exposure to a harmless antigen.
Regulatory CD4(+) T cells are known to develop during the induction of donor-specific peripheral tolerance to transplanted tissues; it is proposed that such tolerance is a consequence of persistent, danger-free stimulation by Ag. To test this hypothesis, male RAG-1(-/-) mice were recolonized with sm...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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2004
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| _version_ | 1797056276427964416 |
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| author | Chen, T Cobbold, S Fairchild, P Waldmann, H |
| author_facet | Chen, T Cobbold, S Fairchild, P Waldmann, H |
| author_sort | Chen, T |
| collection | OXFORD |
| description | Regulatory CD4(+) T cells are known to develop during the induction of donor-specific peripheral tolerance to transplanted tissues; it is proposed that such tolerance is a consequence of persistent, danger-free stimulation by Ag. To test this hypothesis, male RAG-1(-/-) mice were recolonized with small numbers of monospecific CD4(+) T cells specific for the male H-2E(k)-restricted Ag Dby. After 6 wk in the male environment, the monospecific CD4(+) T cells, having recolonized the host, had become anergic to stimulation in vitro and had acquired a regulatory capacity. CD4(+) T cells in these mice expressed higher levels of CTLA-4 and glucocorticoid-induced TNF-related receptor than naive CD4(+) T cells, but only 3% of the recolonizing cells were CD25(+) and did not express significant foxP3 mRNA. In vivo, these tolerant T cells could censor accumulation of, and IFN-gamma production by, naive T cells, with only a slight inhibition of proliferation. This suppressive effect was not reversed by the addition of fresh bone marrow-derived male dendritic cells. These results suggest that persistent exposure to Ag in conditions that fail to evoke proinflammatory stimuli leads to the development of T cells that are both anergic and regulatory. |
| first_indexed | 2024-03-06T19:21:05Z |
| format | Journal article |
| id | oxford-uuid:1a1d066b-b5be-44c8-b1fb-62d11b00d63e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:21:05Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:1a1d066b-b5be-44c8-b1fb-62d11b00d63e2022-03-26T10:52:57ZGeneration of anergic and regulatory T cells following prolonged exposure to a harmless antigen.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1a1d066b-b5be-44c8-b1fb-62d11b00d63eEnglishSymplectic Elements at Oxford2004Chen, TCobbold, SFairchild, PWaldmann, HRegulatory CD4(+) T cells are known to develop during the induction of donor-specific peripheral tolerance to transplanted tissues; it is proposed that such tolerance is a consequence of persistent, danger-free stimulation by Ag. To test this hypothesis, male RAG-1(-/-) mice were recolonized with small numbers of monospecific CD4(+) T cells specific for the male H-2E(k)-restricted Ag Dby. After 6 wk in the male environment, the monospecific CD4(+) T cells, having recolonized the host, had become anergic to stimulation in vitro and had acquired a regulatory capacity. CD4(+) T cells in these mice expressed higher levels of CTLA-4 and glucocorticoid-induced TNF-related receptor than naive CD4(+) T cells, but only 3% of the recolonizing cells were CD25(+) and did not express significant foxP3 mRNA. In vivo, these tolerant T cells could censor accumulation of, and IFN-gamma production by, naive T cells, with only a slight inhibition of proliferation. This suppressive effect was not reversed by the addition of fresh bone marrow-derived male dendritic cells. These results suggest that persistent exposure to Ag in conditions that fail to evoke proinflammatory stimuli leads to the development of T cells that are both anergic and regulatory. |
| spellingShingle | Chen, T Cobbold, S Fairchild, P Waldmann, H Generation of anergic and regulatory T cells following prolonged exposure to a harmless antigen. |
| title | Generation of anergic and regulatory T cells following prolonged exposure to a harmless antigen. |
| title_full | Generation of anergic and regulatory T cells following prolonged exposure to a harmless antigen. |
| title_fullStr | Generation of anergic and regulatory T cells following prolonged exposure to a harmless antigen. |
| title_full_unstemmed | Generation of anergic and regulatory T cells following prolonged exposure to a harmless antigen. |
| title_short | Generation of anergic and regulatory T cells following prolonged exposure to a harmless antigen. |
| title_sort | generation of anergic and regulatory t cells following prolonged exposure to a harmless antigen |
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