Epigenetic quantification of immunosenescent CD8 TEMRA cells in human blood.

Age-related changes in human T-cell populations are important contributors to immunosenescence. In particular, terminally differentiated CD8 effector memory CD45RA TEMRA cells and their subsets have characteristics of cellular senescence, accumulate in older individuals, and are increased in age-related chronic inflammatory diseases. In a detailed T-cell profiling among individuals over 65 years of age, we found a high interindividual variation among CD8 TEMRA populations. CD8 TEMRA proportions correlated positively with cytomegalovirus (CMV) antibody levels, however, not with the chronological age. In the analysis of over 90 inflammation proteins, we identified plasma TRANCE/RANKL levels to associate with several differentiated T-cell populations, including CD8 TEMRA and its CD28 subsets. Given the strong potential of CD8 TEMRA cells as a biomarker for immunosenescence, we used deep-amplicon bisulfite sequencing to match their frequencies in flow cytometry with CpG site methylation levels and developed a computational model to predict CD8 TEMRA cell proportions from whole blood genomic DNA. Our findings confirm the association of CD8 TEMRA and its subsets with CMV infection and provide a novel tool for their high throughput epigenetic quantification as a biomarker of immunosenescence.