Survival tricks

Bird, Lucy

doi:10.1038/nri2442

Research Highlight
Published: November 2008

T cells

Survival tricks

Lucy Bird

Nature Reviews Immunology volume 8, page 825 (2008)Cite this article

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Compared with wild-type mice, Irgm1^−/− mice are known to be more susceptible to infection with various intracellular pathogens, and this susceptibility is associated with profound lymphopenia. The authors reasoned that this might be due, in part, to impaired survival of effector T cells. Indeed, in vitro analysis revealed that Irgm1^−/− CD4⁺ T cells had poor proliferative capacity and reduced survival following T-cell receptor stimulation. These defects were shown to be IFNγ dependent, as T cells from mice lacking both IRGM1 and IFNγ had normal proliferative capacity and survival. In contrast to Irgm1^−/− mice, the Irgm1^−/− Ifng^−/− mice survived an otherwise lethal infection with Mycobacterium avium and did not develop lymphopenia, which indicates that IRGM1 might be required to protect lymphocytes from inhibition mediated by IFNγ.

Further investigation of the mechanism of IFNγ-mediated suppression of Irgm1^−/− T-cell numbers indicated that increased cell death, rather than decreased cell division, was responsible. Interestingly, the mechanism of cell death was found to involve autophagy: IFNγ-exposed Irgm1^−/− T cells contained more membrane-bound vacuoles that closely resembled autophagosomes than Irgm1^−/− Ifng^−/− T cells. In addition, IFNγ-induced death of Irgm1^−/− T cells could be prevented by treatment with inhibitors of phosphoinositide 3-kinase or by knockdown of expression of beclin-1, two proteins that are known to be involved in autophagy.

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ORIGINAL RESEARCH PAPER

Feng, C. G. et al. The immunity-related GTPase Irgm1 promotes the expansion of activated CD4⁺ T cell populations by preventing interferon-γ-induced cell death. Nature Immunol. 21 September 2008 (doi:10.1038/ni.1653)
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