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CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell-intrinsic and cell-extrinsic mechanisms.

ABSTRACT: The inhibitory immunoregulatory receptor CTLA-4 is critical in maintaining self-tolerance, but the mechanisms of its actions have remained controversial. Here we examined the antigen specificity of tissue-infiltrating CD4(+) T cells in Ctla4(-/-) mice. After adoptive transfer, T cells isolated from tissues of Ctla4(-/-) mice showed T cell antigen receptor (TCR)-dependent accumulation in the tissues from which they were derived, which suggested reactivity to tissue-specific antigens. We identified the pancreas-specific enzyme PDIA2 as an autoantigen in Ctla4(-/-) mice. CTLA-4 expressed either on PDIA2-specific effector cells or on regulatory T cells was sufficient to control tissue destruction mediated by PDIA2-specific T cells. Our results demonstrate that both cell-intrinsic and non-cell-autonomous actions of CTLA-4 operate to maintain T cell tolerance to a self antigen.

SUBMITTER: Ise W

PROVIDER: S-EPMC3235641 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell-intrinsic and cell-extrinsic mechanisms.

Ise Wataru W Kohyama Masako M Nutsch Katherine M KM Lee Hyang Mi HM Suri Anish A Unanue Emil R ER Murphy Theresa L TL Murphy Kenneth M KM

Nature immunology 20091227 2

The inhibitory immunoregulatory receptor CTLA-4 is critical in maintaining self-tolerance, but the mechanisms of its actions have remained controversial. Here we examined the antigen specificity of tissue-infiltrating CD4(+) T cells in Ctla4(-/-) mice. After adoptive transfer, T cells isolated from tissues of Ctla4(-/-) mice showed T cell antigen receptor (TCR)-dependent accumulation in the tissues from which they were derived, which suggested reactivity to tissue-specific antigens. We identifie ...[more]

PMID: 20037585

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Dataset Information

CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell-intrinsic and cell-extrinsic mechanisms.

Publications

CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell-intrinsic and cell-extrinsic mechanisms.

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