eLife | |
Autophagy is a critical regulator of memory CD8+ T cell formation | |
Vincenzo Cerundolo1  Alain RM Townsend1  Isabel Panse1  Hanlin Zhang1  Alexander S Watson1  Daniel J Puleston1  Elina Lipina1  Anna Katharina Simon1  Timothy J Powell1  Paul Klenerman2  Stuart Sims2  | |
[1] MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom;Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom; | |
关键词: autophagy; memory T cell; vaccination; ageing; spermidine; influenza; | |
DOI : 10.7554/eLife.03706 | |
来源: DOAJ |
【 摘 要 】
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.
【 授权许可】
Unknown