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

Humphreys, Ian R. ORCID:, Clement, Mathew ORCID:, Marsden, Morgan, Ladell, Kristin Ingrid ORCID:, McLaren, James Edward ORCID:, Smart, Kathryn, Hindley, James Philip, Bridgeman, Hayley, van den Berg, Hugo A., Price, David ORCID:, Ager, Ann ORCID:, Wooldridge, Linda, Godkin, Andrew James ORCID: and Gallimore, Awen Myfanwy ORCID: 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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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: 27 Jul 2023 01:08

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