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

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., Caserta, S., Thomas, D., Davies, K. A., Smith, H., & 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
• 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
• Contract Date: Feb 22, 2018