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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.<\/jats:p>","DOI":"10.7554\/elife.03706","type":"journal-article","created":{"date-parts":[[2014,11,10]],"date-time":"2014-11-10T04:39:42Z","timestamp":1415594382000},"source":"Crossref","is-referenced-by-count":333,"title":["Autophagy is a critical regulator of memory CD8+ T cell formation"],"prefix":"10.7554","volume":"3","author":[{"given":"Daniel J","family":"Puleston","sequence":"first","affiliation":[{"name":"MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlin","family":"Zhang","sequence":"additional","affiliation":[{"name":"MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United 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