Impact of age, sex and CMV-infection on peripheral T cell phenotypes: results from the Berlin BASE-II Study

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.

Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection

“…This cell phenotype has been associated with a poor response to influenza vaccination (39, 40, 154), and it has been suggested that it has some similarities with replicative senescence (155). It has also been shown that CMV infection contributes to the accumulation of these cells (156, 157). In addition to CD8 + CD28 − cells impacting vaccine response, late-stage differentiated CD4 + T-cells, lacking CCR7, CD27, and CD28 and re-expressing CD45RA are also found in CMV-seropositive subjects and correlated with poor vaccination response (158).…”

Human Stem Cell-like Memory T Cells Are Maintained in a State of Dynamic Flux

“…It is established that T SCM cells persist at stable frequencies throughout the human lifespan (Di Benedetto et al., 2015). However, the mechanisms that underlie this remarkable longevity are incompletely defined.…”

Influenza vaccine-mediated protection in older adults: Impact of influenza infection, cytomegalovirus serostatus and vaccine dosage

“…In the absence of perforin, GrB accumulates and has been shown to cause degradation of the extracellular matrix and stimulate an inflammatory response (Hiebert et al, 2011; Parkinson et al, 2015). CMV in older adults has been linked to increased levels of late differentiated T-cells (CD8 + CD28 − ) (Di Benedetto et al, 2015; van der Heiden et al, 2016) and a decline in the effector memory CD8 + T-cell response to influenza (Xie and McElhaney, 2007). Furthermore, the frequency of late differentiated effector T-cells correlates with bGrB activity (McElhaney et al, 2012; Haq et al, 2016).…”