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CMV-specific T-cell responses at older ages: broad responses with a large central memory component may be key to long-term survival

Bajwa, Martha; Vita, Serena; Vescovini, Rosanna; Larsen, Martin; Sansoni, Paolo; Terrazzini, Nadia; Caserta, Stefano; Thomas, David; Davies, Kevin A.; Smith, Helen; Kern, Florian

Authors

Martha Bajwa

Serena Vita

Rosanna Vescovini

Martin Larsen

Paolo Sansoni

Nadia Terrazzini

David Thomas

Kevin A. Davies

Helen Smith

Florian Kern



Abstract

© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. Cytomegalovirus (CMV) infection sometimes causes large expansions of CMV-specific T cells, particularly in older people. This is believed to undermine immunity to other pathogens and to accelerate immunosenescence. While multiple different CMV proteins are recognized, most publications on age-related T-cell expansions have focused on dominant target proteins UL83 or UL123, and the T-cell activation marker interferon-γ (IFN-γ). We were concerned that this narrow approach might have skewed our understanding of CMV-specific immunity at older ages. We have, therefore, widened the scope of analysis to include in vitro–induced T-cell responses to 19 frequently recognized CMV proteins in “young” and “older” healthy volunteers and a group of “oldest old” long-term survivors ( > 85 years of age). Polychromatic flow cytometry was used to analyze T-cell activation markers (CD107, CD154, interleukin-2 [IL-2], tumor necrosis factor [TNF] , and IFN-γ) and memory phenotypes (CD27, CD45RA). The older group had, on average, larger T-cell responses than the young, but, interestingly, response size differences were relatively smaller when all activation markers were considered rather than IFN-γ or TNF alone. The oldest old group recognized more proteins on average than the other groups, and had even bigger T-cell responses than the older group with a significantly larger central memory CD4 T-cell component.

Citation

Bajwa, M., Vita, S., Vescovini, R., Larsen, M., Sansoni, P., Terrazzini, N., …Kern, F. (2017). CMV-specific T-cell responses at older ages: broad responses with a large central memory component may be key to long-term survival. The journal of infectious diseases : official publication of the Infectious Diseases Society of America, 215(8), 1212-1220. https://doi.org/10.1093/infdis/jix080

Journal Article Type Article
Acceptance Date Dec 7, 2017
Online Publication Date Feb 12, 2017
Publication Date Apr 15, 2017
Deposit Date Feb 22, 2018
Publicly Available Date Mar 9, 2018
Journal Journal of Infectious Diseases
Print ISSN 0022-1899
Electronic ISSN 1537-6613
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 215
Issue 8
Pages 1212-1220
DOI https://doi.org/10.1093/infdis/jix080
Keywords Immunology and Allergy; Infectious Diseases
Public URL https://hull-repository.worktribe.com/output/620089
Publisher URL https://academic.oup.com/jid/article/215/8/1212/2990214

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