Epigenetic quantification of immunosenescent CD8+ TEMRA cells in human blood. Issue 5 (9th April 2022)

• Record Type: Journal Article
• Authors: Salumets, Ahto; Tserel, Liina; Rumm, Anna P.; Türk, Lehte; Kingo, Külli; Saks, Kai; Oras, Astrid; Uibo, Raivo; Tamm, Riin; Peterson, Hedi; Kisand, Kai; Peterson, Pärt
• Is Part Of: Aging cell. Volume 21:Issue 5(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-04-09
• Subjects: biomarkers -- CD8+ T‐cells -- CMV -- epigenetics -- human aging -- inflammation; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.13607
• Languages: English
• ISSNs: 1474-9718

Abstract

Abstract: 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. Abstract : We studied old individuals over 65 years of age. We studied their CD4 + and CD8 + T cell subpopulations, quantified the CMV‐specific antibodies, inflammation‐associated proteins, and DNA methylation levels of selected CpGs. Based on our data we developed an epigenetic model to estimate CD8 + TEMRA cell levels in whole blood. The figure was created with BioRender.com.