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In addition, by the peak of expansion, they form precursors to memory T cells capable of self-renewal and indefinite survival. Using lymphocytic choriomeningitis virus Armstrong to probe the response to infection, we found that Foxo1\u2212\/\u2212 CD8+ T cells expand normally with no defects in effector differentiation, but continue to exhibit characteristics of effector T cells long after antigen clearance. The KLRG1lo CD8+ T cells that are normally enriched for memory-precursor cells retain Granzyme B and CD69 expression, and fail to up-regulate TCF7, EOMES, and other memory signature genes. As a correlate, Foxo1\u2212\/\u2212 CD8+ T cells were virtually unable to expand upon secondary infection. Collectively, these results demonstrate an intrinsic role for FOXO1 in establishing the post-effector memory program that is essential to forming long-lived memory cells capable of immune reactivation.<\/jats:p>","DOI":"10.1084\/jem.20130392","type":"journal-article","created":{"date-parts":[[2013,5,28]],"date-time":"2013-05-28T01:00:41Z","timestamp":1369702841000},"page":"1189-1200","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":227,"title":["Differentiation of CD8 memory T cells depends on Foxo1"],"prefix":"10.1084","volume":"210","author":[{"given":"Rodrigo Hess","family":"Michelini","sequence":"first","affiliation":[{"name":"Molecular Biology Section, Division of Biological Sciences 1 and 2"},{"name":"Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 1 and 2"},{"name":"Molecular Biology Section, Division of Biological Sciences 1 and 2"},{"name":"Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew L.","family":"Doedens","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, Division of Biological Sciences 1 and 2"},{"name":"Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananda W.","family":"Goldrath","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, Division of Biological Sciences 1 and 2"},{"name":"Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Hedrick","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, Division of Biological Sciences 1 and 2"},{"name":"Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 1 and 2"},{"name":"Molecular Biology Section, Division of Biological Sciences 1 and 2"},{"name":"Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2013,5,27]]},"reference":[{"key":"2023072601545031000_bib1","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.bone.2011.05.023","article-title":"Unraveling the role of FoxOs in bone\u2014insights from mouse models","volume":"49","author":"Almeida","year":"2011","journal-title":"Bone."},{"key":"2023072601545031000_bib2","doi-asserted-by":"publisher","first-page":"27298","DOI":"10.1074\/jbc.M702811200","article-title":"Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factor- to forkhead box O-mediated transcription","volume":"282","author":"Almeida","year":"2007","journal-title":"J. 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