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- Publisher Website: 10.1084/jem.192.2.303
- Scopus: eid_2-s2.0-0034679560
- PMID: 10899917
- WOS: WOS:000088261100017
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Article: Immunologic self-tolerance maintained by CD25+CD4+ regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4
Title | Immunologic self-tolerance maintained by CD25<sup>+</sup>CD4<sup>+</sup> regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4 |
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Authors | |
Keywords | Autoimmune disease Regulatory T cell Self-tolerance CTLA-4 Cd25 |
Issue Date | 2000 |
Citation | Journal of Experimental Medicine, 2000, v. 192, n. 2, p. 303-310 How to Cite? |
Abstract | This report shows that cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a key role in T cell-mediated dominant immunologic self- tolerance. In vivo blockade of CTLA-4 for a limited period in normal mice leads to spontaneous development of chronic organ-specific autoimmune diseases, which are immunopathologically similar to human counterparts. In normal naive mice, CTLA-4 is constitutively expressed on CD25+CD4+ T cells, which constitute 5-10% of peripheral CD4+ T cells. When the CD25+CD4+ T cells are stimulated via the T cell receptor in vitro, they potently suppress antigen-specific and polyclonal activation and proliferation of other T cells, including CTLA-4-deficient T cells, and blockade of CTLA-4 abrogates the suppression. CD28-deficient CD25+CD4+ T cells can also suppress normal T cells, indicating that CD28 is dispensable for activation of the regulatory T cells. Thus, the CD25+CD4+ regulatory T cell population engaged in dominant self-tolerance may require CTLA-4 but not CD28 as a costimulatory molecule for its functional activation. Furthermore, interference with this role of CTLA-4 suffices to elicit autoimmune disease in otherwise normal animals, presumably through affecting CD25+CD4+ T cell-mediated control of self-reactive T cells. This unique function of CTLA-4 could be exploited to potentiate T cell-mediated immunoregulation, and thereby to induce immunologic tolerance or to control autoimmunity. |
Persistent Identifier | http://hdl.handle.net/10722/291543 |
ISSN | 2023 Impact Factor: 12.6 2023 SCImago Journal Rankings: 6.838 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Takahashi, Takeshi | - |
dc.contributor.author | Tagami, Tomoyuki | - |
dc.contributor.author | Yamazaki, Sayuri | - |
dc.contributor.author | Uede, Toshimitsu | - |
dc.contributor.author | Shimizu, Jun | - |
dc.contributor.author | Sakaguchi, Noriko | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Sakaguchi, Shimon | - |
dc.date.accessioned | 2020-11-17T14:54:36Z | - |
dc.date.available | 2020-11-17T14:54:36Z | - |
dc.date.issued | 2000 | - |
dc.identifier.citation | Journal of Experimental Medicine, 2000, v. 192, n. 2, p. 303-310 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.uri | http://hdl.handle.net/10722/291543 | - |
dc.description.abstract | This report shows that cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a key role in T cell-mediated dominant immunologic self- tolerance. In vivo blockade of CTLA-4 for a limited period in normal mice leads to spontaneous development of chronic organ-specific autoimmune diseases, which are immunopathologically similar to human counterparts. In normal naive mice, CTLA-4 is constitutively expressed on CD25+CD4+ T cells, which constitute 5-10% of peripheral CD4+ T cells. When the CD25+CD4+ T cells are stimulated via the T cell receptor in vitro, they potently suppress antigen-specific and polyclonal activation and proliferation of other T cells, including CTLA-4-deficient T cells, and blockade of CTLA-4 abrogates the suppression. CD28-deficient CD25+CD4+ T cells can also suppress normal T cells, indicating that CD28 is dispensable for activation of the regulatory T cells. Thus, the CD25+CD4+ regulatory T cell population engaged in dominant self-tolerance may require CTLA-4 but not CD28 as a costimulatory molecule for its functional activation. Furthermore, interference with this role of CTLA-4 suffices to elicit autoimmune disease in otherwise normal animals, presumably through affecting CD25+CD4+ T cell-mediated control of self-reactive T cells. This unique function of CTLA-4 could be exploited to potentiate T cell-mediated immunoregulation, and thereby to induce immunologic tolerance or to control autoimmunity. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Experimental Medicine | - |
dc.subject | Autoimmune disease | - |
dc.subject | Regulatory T cell | - |
dc.subject | Self-tolerance | - |
dc.subject | CTLA-4 | - |
dc.subject | Cd25 | - |
dc.title | Immunologic self-tolerance maintained by CD25<sup>+</sup>CD4<sup>+</sup> regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4 | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1084/jem.192.2.303 | - |
dc.identifier.pmid | 10899917 | - |
dc.identifier.pmcid | PMC2193248 | - |
dc.identifier.scopus | eid_2-s2.0-0034679560 | - |
dc.identifier.volume | 192 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 303 | - |
dc.identifier.epage | 310 | - |
dc.identifier.isi | WOS:000088261100017 | - |
dc.identifier.issnl | 0022-1007 | - |