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

被引：92

作者：

Feng, Carl G. ^{[1
]}

Zheng, Lixin ^{[2
]}

Jankovic, Dragana ^{[1
]}

Bafica, Andre ^{[1
]}

Cannons, Jennifer L. ^{[3
]}

Watford, Wendy T. ^{[4
]}

Chaussabel, Damien ^{[5
]}

Hieny, Sara ^{[1
]}

Caspar, Patricia ^{[1
]}

Schwartzberg, Pamela L. ^{[3
]}

Lenardo, Michael J. ^{[2
]}

Sher, Alan ^{[1
]}

机构：

[1] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA

[2] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA

[3] NHGRI, NIH, Bethesda, MD 20892 USA

[4] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA

[5] Baylor Inst Immunol Res, Dallas, TX 75204 USA

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 11期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/ni.1653

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1279 / 1287

页数：9

共 49 条

[1] SOCS1 is a critical inhibitor of interferon γ signaling and prevents the potentially fatal neonatal actions of this cytokine [J].