Autophagy is essential for effector CD8+ T cell survival and memory formation

Abstract

Autophagy has essential roles in cellular energy mobilization and homeostasis, but its role in T cell memory formation is remains poorly understood. Ahmed and colleagues demonstrate that autophagy is critical for the survival of cytotoxic memory cells. The importance of autophagy in the generation of memory CD8+ T cells in vivo is not well defined. We report here that autophagy was dynamically regulated in virus-specific CD8+ T cells during acute infection of mice with lymphocytic choriomeningitis virus. In contrast to the current paradigm, autophagy decreased in activated proliferating effector CD8+ T cells and was then upregulated when the cells stopped dividing just before the contraction phase. Consistent with those findings, deletion of the gene encoding either of the autophagy-related molecules Atg5 or Atg7 had little to no effect on the proliferation and function of effector cells, but these autophagy-deficient effector cells had survival defects that resulted in compromised formation of memory T cells. Our studies define when autophagy is needed during effector and memory differentiation and warrant reexamination of the relationship between T cell activation and autophagy.