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dc.contributor.authorUhrlaub, J.L.
dc.contributor.authorJergović, M.
dc.contributor.authorBradshaw, C.M.
dc.contributor.authorSonar, S.
dc.contributor.authorCoplen, C.P.
dc.contributor.authorDudakov, J.
dc.contributor.authorMurray, K.O.
dc.contributor.authorLanteri, M.C.
dc.contributor.authorBusch, M.P.
dc.contributor.authorvan den Brink, M.R.M.
dc.contributor.authorNikolich-Žugich, J.
dc.date.accessioned2022-04-11T23:17:44Z
dc.date.available2022-04-11T23:17:44Z
dc.date.issued2022
dc.identifier.citationUhrlaub, J. L., Jergović, M., Bradshaw, C. M., Sonar, S., Coplen, C. P., Dudakov, J., Murray, K. O., Lanteri, M. C., Busch, M. P., van den Brink, M. R. M., & Nikolich-Žugich, J. (2022). Quantitative restoration of immune defense in old animals determined by naive antigen-specific CD8 T-cell numbers. Aging Cell.
dc.identifier.issn1474-9718
dc.identifier.doi10.1111/acel.13582
dc.identifier.urihttp://hdl.handle.net/10150/663916
dc.description.abstractOlder 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 Tn cells by treating C57BL/6 mice with IL-7 complexes (IL-7C, anti-IL-7 mAb bound to IL-7), shown previously to efficiently increase peripheral T-cell numbers by homeostatic proliferation. T cells underwent robust expansion following IL-7C administration to old mice increasing the number of total T cells (>fourfold) and NS4b:H-2Db-restricted antigen-specific CD8 T cells (twofold). This improved the numbers of NS4b-specific CD8 T cells detected at the peak of the response against WNV, but not survival of WNV challenge. IL-7C-treated old animals also showed no improvement in WNV-specific effector immunity (neutralizing antibody and in vivo T-cell cytotoxicity). To test quantitative limits to which CD8 Tn cell restoration could improve protective immunity, we transferred graded doses of Ag-specific precursors into old mice and showed that injection of 5400 (but not of 1800 or 600) adult naive WNV-specific CD8 T 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. © 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
dc.language.isoen
dc.publisherJohn Wiley and Sons Inc
dc.rightsCopyright © 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectIL-7/ CD8 T cells
dc.subjectimmune aging
dc.subjectimmune rejuvenation
dc.titleQuantitative restoration of immune defense in old animals determined by naive antigen-specific CD8 T-cell numbers
dc.typeArticle
dc.typetext
dc.contributor.departmentDepartment of Immunobiology, University of Arizona College of Medicine
dc.contributor.departmentUniversity of Arizona Center on Aging, University of Arizona, College of Medicine
dc.identifier.journalAging Cell
dc.description.noteOpen access journal
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
dc.eprint.versionFinal published version
dc.source.journaltitleAging Cell
refterms.dateFOA2022-04-11T23:17:44Z


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Copyright © 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License.
Except where otherwise noted, this item's license is described as Copyright © 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License.