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

Humphreys, Ian R. ORCID: https://orcid.org/0000-0002-9512-5337, Clement, Mathew ORCID: https://orcid.org/0000-0002-9280-5281, Marsden, Morgan, Ladell, Kristin Ingrid ORCID: https://orcid.org/0000-0002-9856-2938, McLaren, James Edward ORCID: https://orcid.org/0000-0002-7021-5934, Smart, Kathryn, Hindley, James Philip, Bridgeman, Hayley, van den Berg, Hugo A., Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Ager, Ann ORCID: https://orcid.org/0000-0002-5763-8908, Wooldridge, Linda, Godkin, Andrew James ORCID: https://orcid.org/0000-0002-1910-7567 and Gallimore, Awen Myfanwy ORCID: https://orcid.org/0000-0001-6675-7004 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:	27 Jul 2023 01:08
URI:	https://orca.cardiff.ac.uk/id/eprint/41462

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