CMV-Specific T-cell Responses at Older Ages: Broad Responses With a Large Central Memory Component May Be Key to Long-term Survival. (12th February 2017)

• Record Type: Journal Article
• Authors: Bajwa, Martha; Vita, Serena; Vescovini, Rosanna; Larsen, Martin; Sansoni, Paolo; Terrazzini, Nadia; Caserta, Stefano; Thomas, David; Davies, Kevin A.; Smith, Helen; Kern, Florian
• Is Part Of: Journal of infectious diseases. Volume 215:Number 8(2017:Apr. 15)
• Page Start: 1212
• Page End: 1220
• Publication Date: 2017-02-12
• Subjects: Cytomegalovirus -- Ageing -- T-cell memory inflation -- T-cells -- Central memory T-cells -- Response breadth.; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix080
• Languages: English
• ISSNs: 0022-1899

Abstract

Summary: CMV-specific T-cell responses expand in older people with response size differences seeming larger when single rather than multiple T-cell functions are measured. The oldest old recognize the most CMV proteins and display an unexpectedly large central memory CD4 T-cell compartment. Abstract: 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.