T cell intrinsic roles of autophagy in promoting adaptive immunity.
Autophagy, an ancient cellular response where autophagic vacuoles are formed within the cytosol, is induced in response to a variety of cellular insults, including growth factor or nutrient withdrawal, organelle damage, and misfolded proteins. Autophagy is rapidly induced in T lymphocytes following antigenic stimulation and blockade of autophagic signaling greatly reduces T cell clonal expansion, suggesting that autophagy is primarily involved in promoting T cell survival. In contrast, a recently identified negative feedback loop involving FADD and caspase-8 limits the level of autophagy in T cells. Failure to activate caspase-8 during T cell mitogenesis leads to hyperactive autophagy and cellular death through a programmed necrotic mechanism. These findings suggest that crosstalk between these cellular processes is essential for T cell activation and homeostasis.
Walsh
Craig M
CM
The Institute for Immunology, University of California, Irvine, CA 92697-3900, USA. cwalsh@uci.edu
Bell
Bryan D
BD
D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy / Q000276:immunology*; D053181:Caspase 8 / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D053200:Fas-Associated Death Domain Protein; D053181:Caspase 8
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