Epigenetic quantification of immunosenescent CD8+ TEMRA cells in human blood

Aging Cell. 2022 May;21(5):e13607. doi: 10.1111/acel.13607. Epub 2022 Apr 9.


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.

Keywords: CD8+ T-cells; CMV; biomarkers; epigenetics; human aging; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CD28 Antigens / metabolism
  • CD8-Positive T-Lymphocytes
  • Cytomegalovirus Infections* / genetics
  • Epigenesis, Genetic
  • Humans
  • Immunologic Memory
  • Immunosenescence*
  • T-Lymphocyte Subsets


  • CD28 Antigens