Abstract
Advancing age is characterized by functional and phenotypic alterations in the distribution of circulating T-cell subsets, some of which are exacerbated by a latent infection with the persistent herpesvirus, cytomegalovirus (CMV). The influence of age, sex and CMV-infection on T-cell subpopulations in the peripheral blood remains incompletely understood. Here, T cells from 157 participants of the Berlin Aging Study II (BASE-II) were characterized at 21–34 (n = 59) and 62–85 (n = 98) years of age. We found that the frequency of naïve CD8+ T cells was significantly lower in the older group than in the young, and was different in men and women. Elderly men had a significantly lower proportion of naïve CD8+ T cells than younger men, regardless of their CMV-status, but in older women, this was seen only in the CMV-seropositive group. Reciprocally, older men had a higher proportion of late-differentiated, potentially “senescent” CD57+ T cells. Thus, T-cell senescence may be more pronounced in older men than women. Within the CD4+ population, in the elderly of both sexes there was a significantly higher proportion of late-differentiated TEMRA cells (T effector memory cells re-expressing CD45RA), but these were present exclusively in CMV-positive subjects. Finally, for the first time, we examined the so-called TSCM cell (T-stem cell-like memory) subpopulations in both CD4+ and CD8+ subsets and found that neither CMV-seropositivity nor age or sex affected their frequencies. This study confirms significant cross-sectional age-associated differences of T-cell subset distribution in a representative German urban population and emphasizes the impact of both sex and CMV-infection on T-cell naïve and memory phenotypes, but unaffected frequencies of T-stem cell-like memory cells.
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Acknowledgments
The authors thank participants and colleagues of the interdisciplinary group of the BASE-II study. We would like to thank Karin Hähnel and Lilly Öttinger for their excellent organizational and technical assistance and Nicole Janssen for performing CMV-ELISAs. We thank all colleagues of the TATI-Group and especially Kilian Wistuba-Hamprecht, whose skills and commitment made this study possible. We gratefully acknowledge the support from the German Ministry for Education and Research Grant Nos. 16SV5536K and FKZ 01EI1401 and from the European Commission Grant FP7 259679, as well as from the Max Planck Institute for Human Development, Berlin.
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10522_2015_9563_MOESM1_ESM.ppt
Supplementary Figure S1: Gating strategy to identify distinct subsets of CD4+ (a) and CD8+ (b) T cells. Viable lymphocytes were gated within the CD3+ gate and selected for CD8+ or CD4+ T cell subsets, which were subdivided into four (N, CM, EM and TEMRA-E) using CD45RA and CCR7. CD27 and CD28 staining was used to characterize their differentiation status: N (CD45RA+CCR7+CD27+CD28+); CM (CD45RA-CCR7+CD27+CD28+); EM3 (CD45RA−CCR7−CD27−CD28−); E (CD45RA+CCR7−CD27−CD28−). N cells have been gated for CD95 to identify TSCM (CD45RA+CCR7+CD27+ CD28+CD95+) cells. Supplementary material 1 (PPT 345 kb)
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Di Benedetto, S., Derhovanessian, E., Steinhagen-Thiessen, E. et al. Impact of age, sex and CMV-infection on peripheral T cell phenotypes: results from the Berlin BASE-II Study. Biogerontology 16, 631–643 (2015). https://doi.org/10.1007/s10522-015-9563-2
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DOI: https://doi.org/10.1007/s10522-015-9563-2