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

Carl G. Feng, Lixin Zheng, Dragana Jankovic, André Báfica, Jennifer L. Cannons, Wendy T. Watford, Damien J. Chaussabel, Sara Hieny, Patricia Caspar, Pamela L. Schwartzberg, Michael J. Lenardo, Alan Sher

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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.

Original languageEnglish
Pages (from-to)1279-1287
Number of pages9
JournalNature Immunology
Volume9
Issue number11
DOIs
Publication statusPublished - 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Feng, C. G., Zheng, L., Jankovic, D., Báfica, A., Cannons, J. L., Watford, W. T., Chaussabel, D. J., Hieny, S., Caspar, P., Schwartzberg, P. L., Lenardo, M. J., & Sher, A. (2008). The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell populations by preventing interferon-γ-induced cell death. Nature Immunology, 9(11), 1279-1287. https://doi.org/10.1038/ni.1653