{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T22:06:55Z","timestamp":1773094015526,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T00:00:00Z","timestamp":1647302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007197","name":"U.S. Public Health Service","doi-asserted-by":"publisher","award":["AG052359"],"award-info":[{"award-number":["AG052359"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007197","name":"U.S. Public Health Service","doi-asserted-by":"publisher","award":["AG020719"],"award-info":[{"award-number":["AG020719"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007197","name":"U.S. Public Health Service","doi-asserted-by":"publisher","award":["AI091816\u201001"],"award-info":[{"award-number":["AI091816\u201001"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Older humans and animals often exhibit reduced immune responses to infection and vaccination, and this often directly correlates to the numbers and frequency of naive T (Tn) cells. We found such a correlation between reduced numbers of blood CD8+ Tn cells and severe clinical outcomes of West Nile virus (WNV) in both humans naturally exposed to, and mice experimentally infected with, WNV. To examine possible causality, we sought to increase the number of CD8\u00a0Tn cells by treating C57BL\/6\u00a0mice with IL\u20107 complexes (IL\u20107C, anti\u2010IL\u20107\u00a0mAb bound to IL\u20107), shown previously to efficiently increase peripheral T\u2010cell numbers by homeostatic proliferation. T cells underwent robust expansion following IL\u20107C administration to old mice increasing the number of total T cells (&gt;fourfold) and NS4b:H\u20102D\n                    <jats:sup>b<\/jats:sup>\n                    \u2010restricted antigen\u2010specific CD8\u00a0T cells (twofold). This improved the numbers of NS4b\u2010specific CD8\u00a0T cells detected at the peak of the response against WNV, but not survival of WNV challenge. IL\u20107C\u2010treated old animals also showed no improvement in WNV\u2010specific effector immunity (neutralizing antibody and in vivo T\u2010cell cytotoxicity). To test quantitative limits to which CD8\u00a0Tn cell restoration could improve protective immunity, we transferred graded doses of Ag\u2010specific precursors into old mice and showed that injection of 5400 (but not of 1800 or 600) adult naive WNV\u2010specific CD8\u00a0T cells significantly increased survival after WNV. These results set quantitative limits to the level of Tn reconstitution necessary to improve immune defense in older organisms and are discussed in light of targets of immune reconstitution.\n                  <\/jats:p>","DOI":"10.1111\/acel.13582","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T03:44:24Z","timestamp":1647315864000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Quantitative restoration of immune defense in old animals determined by naive antigen\u2010specific CD8 T\u2010cell numbers"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7745-0179","authenticated-orcid":false,"given":"Jennifer L.","family":"Uhrlaub","sequence":"first","affiliation":[{"name":"Department of Immunobiology University of Arizona College of Medicine  Tucson Arizona USA"},{"name":"University of Arizona Center on Aging University of Arizona College of Medicine, Tucson  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7630-1219","authenticated-orcid":false,"given":"Mladen","family":"Jergovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Immunobiology University of Arizona College of Medicine  Tucson Arizona USA"},{"name":"University of Arizona Center on Aging University of Arizona College of Medicine, Tucson  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7835-9326","authenticated-orcid":false,"given":"Christine M.","family":"Bradshaw","sequence":"additional","affiliation":[{"name":"Department of Immunobiology University of Arizona College of Medicine  Tucson Arizona USA"},{"name":"University of Arizona Center on Aging University of Arizona College of Medicine, Tucson  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandip","family":"Sonar","sequence":"additional","affiliation":[{"name":"Department of Immunobiology University of Arizona College of Medicine  Tucson Arizona USA"},{"name":"University of Arizona Center on Aging University of Arizona College of Medicine, Tucson  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher P.","family":"Coplen","sequence":"additional","affiliation":[{"name":"Department of Immunobiology University of Arizona College of Medicine  Tucson Arizona USA"},{"name":"University of Arizona Center on Aging University of Arizona College of Medicine, Tucson  Tucson Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarrod","family":"Dudakov","sequence":"additional","affiliation":[{"name":"Program in Immunology Clinical Research Division, and Immunotherapy Integrated Research Center Fred Hutchinson Cancer Research Center  Seattle Washington USA"},{"name":"Department of Immunology University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristy O.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Section of Pediatric Tropical Medicine and National School of Tropical Medicine Baylor College of Medicine  Houston Texas USA"},{"name":"William T. 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