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- Title
The immunity-related GTPase Irgm1 promotes the expansion of activated CD4<sup>+</sup> T cell populations by preventing interferon-γ-induced cell death.
- Authors
Feng, Carl G; Zheng, Lixin; Jankovic, Dragana; Báfica, André; Cannons, Jennifer L; Watford, Wendy T; Chaussabel, Damien; Hieny, Sara; Caspar, Patricia; Schwartzberg, Pamela L; Lenardo, Michael J; Sher, Alan
- Abstract
Mice deficient in the interferon-γ (IFN-γ)-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-γ-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-γ-induced autophagic cell death. Mice deficient in both IFN-γ 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-γ on effector T lymphocyte survival while promoting the antimicrobial functions of IFN-γ.
- Publication
Nature Immunology, 2008, Vol 9, Issue 11, p1279
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.1653