Autophagy is a critical regulator of memory CD8(+) T cell formation

作者：Puleston Daniel J^*; Zhang Hanlin; Powell Timothy J; Lipina Elina; Sims Stuart; Panse Isabel; Watson Alexander S; Cerundolo Vincenzo; Townsend Alain R M; Klenerman Paul; Simon Anna Katharina

来源：eLife, 2014, 3: e03706.

DOI：10.7554/eLife.03706

During infection, CD8(+) T cells initially expand then contract, leaving a small memory pool providing long lasting immunity. While it has been described that CD8(+) T cell memory formation becomes defective in old age, the cellular mechanism is largely unknown. Autophagy is a major cellular lysosomal degradation pathway of bulk material, and levels are known to fall with age. In this study, we describe a novel role for autophagy in CD8(+) T cell memory formation. Mice lacking the autophagy gene Atg7 in T cells failed to establish CD8(+) T cell memory to influenza and MCMV infection. Interestingly, autophagy levels were diminished in CD8(+) T cells from aged mice. We could rejuvenate CD8(+) T cell responses in elderly mice in an autophagy dependent manner using the compound spermidine. This study reveals a cell intrinsic explanation for poor CD8(+) T cell memory in the elderly and potentially offers novel immune modulators to improve aged immunity.

• 出版日期2014-11-11