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

eLife

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