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The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell populations by preventing interferon-gamma-induced cell death.

ABSTRACT: Mice deficient in the interferon-gamma (IFN-gamma)-inducible, immunity-related GTPase Irgm1 have defective host resistance to a variety of intracellular pathogens. This greater susceptibility to infection is associated with impaired IFN-gamma-dependent macrophage microbicidal activity in vitro. Here we show that Irgm1 also regulated the survival of mature effector CD4(+) T lymphocytes by protecting them from IFN-gamma-induced autophagic cell death. Mice deficient in both IFN-gamma and Irgm1 were 'rescued' from the lymphocyte depletion and greater mortality that occurs in mice singly deficient in Irgm1 after mycobacterial infection. Our studies identify a feedback mechanism in the T helper type 1 response that limits the detrimental effects of IFN-gamma on effector T lymphocyte survival while promoting the antimicrobial functions of IFN-gamma.

SUBMITTER: Feng CG

PROVIDER: S-EPMC2580721 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell populations by preventing interferon-gamma-induced cell death.

Feng Carl G CG Zheng Lixin L Jankovic Dragana D Báfica André A Cannons Jennifer L JL Watford Wendy T WT Chaussabel Damien D Hieny Sara S Caspar Patricia P Schwartzberg Pamela L PL Lenardo Michael J MJ Sher Alan A

Nature immunology 20080921 11

Mice deficient in the interferon-gamma (IFN-gamma)-inducible, immunity-related GTPase Irgm1 have defective host resistance to a variety of intracellular pathogens. This greater susceptibility to infection is associated with impaired IFN-gamma-dependent macrophage microbicidal activity in vitro. Here we show that Irgm1 also regulated the survival of mature effector CD4(+) T lymphocytes by protecting them from IFN-gamma-induced autophagic cell death. Mice deficient in both IFN-gamma and Irgm1 were ...[more]

PMID: 18806793

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Dataset Information

The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell populations by preventing interferon-gamma-induced cell death.

Publications

The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell populations by preventing interferon-gamma-induced cell death.

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