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.