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Cell Death Differ. 2012 Jan;19(1):144-52. doi: 10.1038/cdd.2011.78. Epub 2011 Jun 10.

Autophagy promotes T-cell survival through degradation of proteins of the cell death machinery.

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  • 1Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Abstract

Autophagy is implicated in regulating cell death in activated T cells, but the underlying mechanism is unclear. Here, we show that inhibition of autophagy via Beclin 1 gene deletion in T cells leads to rampant apoptosis in these cells upon TCR stimulation. Beclin 1-deficient mice fail to mount autoreactive T-cell responses and are resistant to experimental autoimmune encephalomyelitis. Compared with Th17 cells, Th1 cells are much more susceptible to cell death upon Beclin 1 deletion. Cell death proteins are highly increased in Beclin 1-deficient T cells and inhibition of caspases and genetic deletion of Bim reverse apoptosis. In addition, p62/sequestosome 1 binds to caspase-8 but does not control levels of procaspase-8 or other cell death-related proteins. These results establish a direct role of autophagy in inhibiting the programmed cell death through degradation of apoptosis proteins in activated T cells.

PMID:
21660048
[PubMed - indexed for MEDLINE]
PMCID:
PMC3252822
Free PMC Article
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