{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:28:12Z","timestamp":1791062892535,"version":"4.1.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2013,2,25]],"date-time":"2013-02-25T00:00:00Z","timestamp":1361750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"U. S. National Institutes of Health","doi-asserted-by":"crossref","award":["P01-A1078897"],"award-info":[{"award-number":["P01-A1078897"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"U. S. National Institutes of Health","doi-asserted-by":"crossref","award":["U19-AI082630"],"award-info":[{"award-number":["U19-AI082630"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"U. S. National Institutes of Health","doi-asserted-by":"crossref","award":["BAA 266200500030C"],"award-info":[{"award-number":["BAA 266200500030C"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,2,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Increased T-bet levels and senescence in CD8 T cells from aged individuals as possible mechanisms for decreased influenza-specific functionality.<\/jats:p>\n               <jats:p>Aged individuals have increased morbidity and mortality following influenza and other viral infections, despite previous exposure or vaccination. Mouse and human studies suggest increased senescence and\/or exhaustion of influenza virus-specific CD8 T cells with advanced age. However, neither the relationship between senescence and exhaustion nor the underlying transcriptional pathways leading to decreased function of influenza virus-specific cellular immunity in elderly humans are well-defined. Here, we demonstrate that increased percentages of CD8 T cells from aged individuals express CD57 and KLRG1, along with PD-1 and other inhibitory receptors, markers of senescence, or exhaustion, respectively. Expression of T-box transcription factors, T-bet and Eomes, were also increased in CD8 T cells from aged subjects and correlated closely with expression of CD57 and KLRG1. Influenza virus-specific CD8 T cells from aged individuals exhibited decreased functionality with corresponding increases in CD57, KLRG1, and T-bet, a molecular regulator of terminal differentiation. However, in contrast to total CD8 T cells, influenza virus-specific CD8 T cells had altered expression of inhibitory receptors, including lower PD-1, in aged compared with young subjects. Thus, our data suggest a prominent role for senescence and\/or terminal differentiation for influenza virus-specific CD8 T cells in elderly subjects.<\/jats:p>","DOI":"10.1189\/jlb.0912438","type":"journal-article","created":{"date-parts":[[2013,2,26]],"date-time":"2013-02-26T05:31:02Z","timestamp":1361856662000},"page":"825-836","source":"Crossref","is-referenced-by-count":81,"title":["Increased T-bet is associated with senescence of influenza virus-specific CD8 T cells in aged humans"],"prefix":"10.1093","volume":"93","author":[{"given":"Douglas V","family":"Dolfi","sequence":"first","affiliation":[{"name":"Institute for Immunology, Department of Microbiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen D","family":"Mansfield","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Department of Microbiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio M","family":"Polley","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Department of Microbiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan A","family":"Doyle","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Medicine, Duke University Medical Center, and Geriatric Research, Education and Clinical Center , Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon J","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanspeter","family":"Pircher","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Freiburg , Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth E","family":"Schmader","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Medicine, Duke University Medical Center, and Geriatric Research, Education and Clinical Center , Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E John","family":"Wherry","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Department of Microbiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,2,25]]},"reference":[{"key":"2023012312533700900_B1","first-page":"1057","article-title":"Estimates of deaths associated with seasonal influenza\u2014United States, 1976\u20132007","volume":"59","author":"Centers for Disease Control and Prevention","year":"2010","journal-title":"Morbidity and Mortality Weekly Report (MMWR)"},{"key":"2023012312533700900_B2","doi-asserted-by":"crossref","first-page":"775","DOI":"10.2217\/ahe.09.69","article-title":"Effects of aging on the adaptive immune response to respiratory virus infections","volume":"5","author":"Fulton","year":"2009","journal-title":"Aging Health"},{"key":"2023012312533700900_B3","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1001\/jama.289.2.179","article-title":"Mortality associated with influenza and respiratory syncytial virus in the United States","volume":"289","author":"Thompson","year":"2003","journal-title":"JAMA"},{"key":"2023012312533700900_B4","doi-asserted-by":"crossref","first-page":"5197","DOI":"10.4049\/jimmunol.159.11.5197","article-title":"CD8+ T cells clear influenza virus by perforin or Fas-dependent processes","volume":"159","author":"Topham","year":"1997","journal-title":"J. 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