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.

Automated summary

Age-related changes in T-cell populations play an important role in immunosenescence. CD8(+) TEMRA cells and their subsets have characteristics of cellular senescence and increase in older individuals and age-related chronic inflammatory diseases. CD8(+) TEMRA proportions correlate with cytomegalovirus (CMV) antibody levels but not with chronological age. TRANCE/RANKL levels are associated with differentiated T-cell populations, including CD8(+) TEMRA and its CD28(-) subsets. Deep-amplicon bisulfite sequencing can be used to predict CD8(+) TEMRA cell proportions as a biomarker of immunosenescence.