Article abstract
Nature Immunology 9, 1279 - 1287 (2008)
Published online: 21 September 2008 | Corrected online: 5 October 2008 | doi:10.1038/ni.1653
The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell populations by preventing interferon-
-induced cell death
Carl G Feng1,6, Lixin Zheng2,6, Dragana Jankovic1, André Báfica1, Jennifer L Cannons3, Wendy T Watford4, Damien Chaussabel5, Sara Hieny1, Patricia Caspar1, Pamela L Schwartzberg3, Michael J Lenardo2 & Alan Sher1
Abstract
Mice deficient in the interferon-
(IFN-)-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--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--induced autophagic cell death. Mice deficient in both IFN- 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- on effector T lymphocyte survival while promoting the antimicrobial functions of IFN-.
- Laboratory of Parasitic Diseases, Bethesda, Maryland 20892, USA.
- Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
- National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
- Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Baylor Institute for Immunology Research, Dallas, Texas 75204, USA.
- These authors contributed equally to this work.
Correspondence to: Carl G Feng1,6 e-mail: cfeng@niaid.nih.gov
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