The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell populations by preventing interferon-gamma-induced cell death.
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.
Feng
Carl G
CG
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. cfeng@niaid.nih.gov
Zheng
Lixin
L
Jankovic
Dragana
D
Báfica
André
A
Cannons
Jennifer L
JL
Watford
Wendy T
WT
Chaussabel
Damien
D
Hieny
Sara
S
Caspar
Patricia
P
Schwartzberg
Pamela L
PL
Lenardo
Michael J
MJ
Sher
Alan
A
D000818:Animals; D001343:Autophagy / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009162:Mycobacterium avium / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology
C096000:Ifi1 protein, mouse; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D019204:GTP-Binding Proteins