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

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, IFN-?. 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, IL-2, TNF, IFN-?) and memory phenotype (CD27, CD45RA). The older 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-? or TNF alone. The oldest old recognized more proteins on average than the other groups and had even bigger T-cell responses than the older with a significantly larger central memory CD4 T-cell component.