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Avidity of influenza-specific memory CD8+ T-cell populations decays over time compromising antiviral immunity
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Humphreys, Ian R., Clement, Mathew, Marsden, Morgan, Ladell, Kristin, McLaren, James E., Smart, Kathryn, Hindley, James P., Bridgeman, Hayley M., Berg, Hugo van den , Price, D. A., Ager, Ann, Wooldridge, Linda, Godkin, Andrew and Gallimore, Awen M. (2012) Avidity of influenza-specific memory CD8+ T-cell populations decays over time compromising antiviral immunity. European Journal of Immunology, Volume 42 (Number 12). pp. 3235-3242. doi:10.1002/eji.201242575
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Official URL: http://dx.doi.org/10.1002/eji.201242575
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: | Journal Article | ||||
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| Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QR Microbiology > QR180 Immunology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Mathematics | ||||
| Library of Congress Subject Headings (LCSH): | Influenza , Cell-mediated cytotoxicity, Vaccination | ||||
| Journal or Publication Title: | European Journal of Immunology | ||||
| Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA | ||||
| ISSN: | 0014-2980 | ||||
| Official Date: | 2012 | ||||
| Dates: |
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| Volume: | Volume 42 | ||||
| Number: | Number 12 | ||||
| Page Range: | pp. 3235-3242 | ||||
| DOI: | 10.1002/eji.201242575 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Open Access | ||||
| Funder: | Wellcome Trust (London, England) | ||||
| Grant number: | WT082249MA, 086983/Z/08/Z (WT) |
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