Normal responsiveness of CTLA-4-deficient anti-viral cytotoxic T cells.
CTLA-4 has been proposed to negatively regulate immune responses, and mice deficient for CTLA-4 expression succumb to a lymphoproliferative disorder within a few weeks after birth. This study assessed the responsiveness of CTLA-4-deficient T cells expressing a class I-restricted TCR specific for lym...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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1998
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| _version_ | 1826282555990605824 |
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| author | Bachmann, M Waterhouse, P Speiser, D McKall-Faienza, K Mak, T Ohashi, P |
| author_facet | Bachmann, M Waterhouse, P Speiser, D McKall-Faienza, K Mak, T Ohashi, P |
| author_sort | Bachmann, M |
| collection | OXFORD |
| description | CTLA-4 has been proposed to negatively regulate immune responses, and mice deficient for CTLA-4 expression succumb to a lymphoproliferative disorder within a few weeks after birth. This study assessed the responsiveness of CTLA-4-deficient T cells expressing a class I-restricted TCR specific for lymphocytic choriomeningitis virus (LCMV). The kinetics of T cell proliferation were studied in vitro after stimulation of T cells with full and partial T cell agonists. No gross abnormalities in CTLA-4-deficient T cells could be detected. Using adoptive transfer experiments, T cell responses were also measured in vivo after infection with LCMV. Low dose infection with LCMV leads to strong expansion of specific T cells followed by a reduction in T cells that parallels the elimination of Ag. The kinetics of T cell expansion and elimination after low dose LCMV infection were not affected by the absence of CTLA-4. High dose infection of mice with LCMV leads to a transient expansion of T cells followed by T cell exhaustion, where all specific T cells are eliminated. T cell exhaustion also occurred in the absence of CTLA-4. Thus, surprisingly, the absence of CTLA-4 did not interfere with T cell activation, down-regulation of ongoing T cell responses after the elimination of Ag, or the exhaustion of T cell responses in the presence of excessive amounts of Ag. |
| first_indexed | 2024-03-07T00:45:38Z |
| format | Journal article |
| id | oxford-uuid:84892af6-a7ad-4c52-b51b-f838131b68aa |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:45:38Z |
| publishDate | 1998 |
| record_format | dspace |
| spelling | oxford-uuid:84892af6-a7ad-4c52-b51b-f838131b68aa2022-03-26T21:51:46ZNormal responsiveness of CTLA-4-deficient anti-viral cytotoxic T cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:84892af6-a7ad-4c52-b51b-f838131b68aaEnglishSymplectic Elements at Oxford1998Bachmann, MWaterhouse, PSpeiser, DMcKall-Faienza, KMak, TOhashi, PCTLA-4 has been proposed to negatively regulate immune responses, and mice deficient for CTLA-4 expression succumb to a lymphoproliferative disorder within a few weeks after birth. This study assessed the responsiveness of CTLA-4-deficient T cells expressing a class I-restricted TCR specific for lymphocytic choriomeningitis virus (LCMV). The kinetics of T cell proliferation were studied in vitro after stimulation of T cells with full and partial T cell agonists. No gross abnormalities in CTLA-4-deficient T cells could be detected. Using adoptive transfer experiments, T cell responses were also measured in vivo after infection with LCMV. Low dose infection with LCMV leads to strong expansion of specific T cells followed by a reduction in T cells that parallels the elimination of Ag. The kinetics of T cell expansion and elimination after low dose LCMV infection were not affected by the absence of CTLA-4. High dose infection of mice with LCMV leads to a transient expansion of T cells followed by T cell exhaustion, where all specific T cells are eliminated. T cell exhaustion also occurred in the absence of CTLA-4. Thus, surprisingly, the absence of CTLA-4 did not interfere with T cell activation, down-regulation of ongoing T cell responses after the elimination of Ag, or the exhaustion of T cell responses in the presence of excessive amounts of Ag. |
| spellingShingle | Bachmann, M Waterhouse, P Speiser, D McKall-Faienza, K Mak, T Ohashi, P Normal responsiveness of CTLA-4-deficient anti-viral cytotoxic T cells. |
| title | Normal responsiveness of CTLA-4-deficient anti-viral cytotoxic T cells. |
| title_full | Normal responsiveness of CTLA-4-deficient anti-viral cytotoxic T cells. |
| title_fullStr | Normal responsiveness of CTLA-4-deficient anti-viral cytotoxic T cells. |
| title_full_unstemmed | Normal responsiveness of CTLA-4-deficient anti-viral cytotoxic T cells. |
| title_short | Normal responsiveness of CTLA-4-deficient anti-viral cytotoxic T cells. |
| title_sort | normal responsiveness of ctla 4 deficient anti viral cytotoxic t cells |
| work_keys_str_mv | AT bachmannm normalresponsivenessofctla4deficientantiviralcytotoxictcells AT waterhousep normalresponsivenessofctla4deficientantiviralcytotoxictcells AT speiserd normalresponsivenessofctla4deficientantiviralcytotoxictcells AT mckallfaienzak normalresponsivenessofctla4deficientantiviralcytotoxictcells AT makt normalresponsivenessofctla4deficientantiviralcytotoxictcells AT ohaship normalresponsivenessofctla4deficientantiviralcytotoxictcells |