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T cell-intrinsic and -extrinsic contributions of the IFNAR/STAT1-axis to thymocyte survival.

ABSTRACT: STAT1 is an essential part of interferon signaling, and STAT1-deficiency results in heightened susceptibility to infections or autoimmunity in both mice and humans. Here we report that mice lacking the IFN?/?-receptor (IFNAR1) or STAT1 display impaired deletion of autoreactive CD4(+)CD8(+)-T-cells. Strikingly, co-existence of WT T cells restored thymic elimination of self-reactive STAT1-deficient CD4(+)CD8(+)-T cells. Analysis of STAT1-deficient thymocytes further revealed reduced Bim expression, which was restored in the presence of WT T cells. These results indicate that type I interferons and STAT1 play an important role in the survival of MHC class I-restricted T cells in a T cell intrinsic and non-cell intrinsic manner that involves regulation of Bim expression through feedback provided by mature STAT1-competent T cells.

SUBMITTER: Moro H

PROVIDER: S-EPMC3176796 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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T cell-intrinsic and -extrinsic contributions of the IFNAR/STAT1-axis to thymocyte survival.

Moro Hiroshi H Otero Dennis C DC Tanabe Yoshinari Y David Michael M

PloS one 20110920 9

STAT1 is an essential part of interferon signaling, and STAT1-deficiency results in heightened susceptibility to infections or autoimmunity in both mice and humans. Here we report that mice lacking the IFNα/β-receptor (IFNAR1) or STAT1 display impaired deletion of autoreactive CD4(+)CD8(+)-T-cells. Strikingly, co-existence of WT T cells restored thymic elimination of self-reactive STAT1-deficient CD4(+)CD8(+)-T cells. Analysis of STAT1-deficient thymocytes further revealed reduced Bim expression ...[more]

PMID: 21949815

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