Age-associated alterations in γδ T-cells are present predominantly in individuals infected with Cytomegalovirus

Background: Despite the common perception that latent Cytomegalovirus (CMV) infection is usually symptom-free, emerging epidemiological evidence suggests that it may in fact be associated with higher mortality over extended follow-up. Mechanisms responsible for this potentially important effect are unclear. CMV infection is known to have a large impact on the distribution of T cell phenotypes, especially the accumulation of late-stage differentiated CD8⁺, as well as Vδ2^- γδ T-cells, which are the main subset of γδ T-cells involved in anti-CMV immunity. Its impact on γδ T-cells in the aging context is less well-defined.Results: Here, we investigated a group of healthy individuals aged between 21 and 89 years, in order to correlate the frequency and differentiation status of γδ T-cells with age. We found that these parameters were only marginally influenced by age, but were marked in people with a latent CMV infection. Thus, we observed a significant age-associated accumulation of late-differentiated T-cells within the Vδ2^- population, but only in CMV-seropositive donors. There was also a strong trend towards reduced frequency of early-differentiated cells within the Vδ2^- phenotype. Older people had significantly higher anti-CMV IgG titers, which in turn correlated significantly with a lower Vδ2⁺/Vδ2^- ratio and a shift from early- to a late-differentiated Vδ2^- T-cell phenotype.Conclusions: Our findings demonstrate a strong influence of CMV on γδ T-cells during human ageing, similar to that observed for αβ T-cells. Differences between donors of different ages are more marked in CMV-infected individuals. The biological implications of this potent age-associated CMV-mediated immune-modulation require clarification.