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.