Phenotypic and functional immune attributes predicting survival in very elderly people (47.7)

Abstract

Abstract The low level of naïve T-cells commonly observed in the elderly is thought to be causally associated with mortality. However this has not been tested in longitudinal studies. Here, we present correlations between peripheral T-cell subsets and 8-year survival in individuals from the population-based prospective Leiden 85-plus Study. Counter-intuitively, a lower frequency of naïve (CD45RA+CCR7+CD27+CD28+) CD8+ T-cells at baseline (>88 years) correlated with significantly better survival, while there was a tendency for the reciprocal accumulation of late-differentiated effector memory cells (CD45RA-CCR7-CD27-CD28-) also to associate with better survival, suggesting that better retention of memory cells specific for previously encountered antigens provided a survival advantage in this particular population. Given the prevalence of Cytomegalovirus (CMV) and its reported association with immunosenescence, we tested whether memory for this potential pathogen was relevant to survival. We found that individuals mounting an exclusively pro-inflammatory ex-vivo response (TNF, IFN-γ, IL-17) to the major CMV target molecules pp65 and IE1 had a significant survival advantage over those also having anti-inflammatory responses (IL-10). These findings suggest that higher levels of naïve T cells are not necessarily associated with a survival advantage and imply that the nature of immunosurveillance against CMV may be crucial for remaining longevity, at least in the very elderly.