Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4.
J Exp Med
; 192(2): 303-10, 2000 Jul 17.
Article
em En
| MEDLINE
| ID: mdl-10899917
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Receptores de Interleucina-2
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Antígenos de Diferenciação
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Imunoconjugados
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Tolerância Imunológica
Tipo de estudo:
Etiology_studies
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Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article