Format

Send to

Choose Destination
Nat Immunol. 2008 Nov;9(11):1279-87. doi: 10.1038/ni.1653. Epub 2008 Sep 21.

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

Author information

1
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. cfeng@niaid.nih.gov

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.

PMID:
18806793
PMCID:
PMC2580721
DOI:
10.1038/ni.1653
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center