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Avidity of influenza-specific memory CD8+T-cell populations decays over time compromising antiviral immunity

Humphreys, Ian R., Clement, Mathew, Marsden, Morgan, Ladell, Kristin Ingrid, McLaren, James Edward, Smart, Kathryn, Hindley, James Philip, Bridgeman, Hayley, van den Berg, Hugo A., Price, David, Ager, Ann, Wooldridge, Linda, Godkin, Andrew James and Gallimore, Awen Myfanwy 2012. Avidity of influenza-specific memory CD8+T-cell populations decays over time compromising antiviral immunity. European Journal of Immunology 42 (12) , pp. 3235-3242. 10.1002/eji.201242575

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Abstract

Decline of cell-mediated immunity is often attributed to decaying T-cell numbers and their distribution in peripheral organs. This study examined the hypothesis that qualitative as well as quantitative changes contribute to the declining efficacy of CD8+ T-cell memory. Using a model of influenza virus infection, where loss of protective CD8+ T-cell immunity was observed 6 months postinfection, we found no decline in antigen-specific T-cell numbers or migration to the site of secondary infection. There was, however, a large reduction in antigen-specific CD8+ T-cell degranulation, cytokine secretion, and polyfunctionality. A profound loss of high-avidity T cells over time indicated that failure to confer protective immunity resulted from the inferior functional capacity of remaining low avidity cells. These data imply that high-avidity central memory T cells wane with declining antigen levels, leaving lower avidity T cells with reduced functional capabilities.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > R Medicine (General)
Uncontrolled Keywords: CD8+ T cell; Cytotoxicity; IFN-γ; Influenza; Vaccination
Publisher: John Wiley & Sons
ISSN: 0014-2980
Last Modified: 12 Sep 2018 21:00
URI: http://orca.cf.ac.uk/id/eprint/41462

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