Peripheral blood T-cell signatures from high-resolution immune phenotyping of γδ and αβ T-cells in younger and older subjects in the Berlin Aging Study II

Background: Aging and latent infection with Cytomegalovirus (CMV) are thought to be major factors driving the immune system towards immunosenescence, primarily characterized by reduced amounts of naive T-cells and increased memory T-cells, potentially associated with higher morbidity and mortality. The composition of both major compartments, gamma delta as well as alpha beta T-cells, is altered by age and CMV, but detailed knowledge of changes to the gamma delta subset is currently limited. Results: Here, we have surveyed a population of 73 younger (23-35 years) and 144 older (62-85 years) individuals drawn from the Berlin Aging Study II, investigating the distribution of detailed differentiation phenotypes of both gamma delta and alpha beta T-cells. Correlation of frequencies and absolute counts of the identified phenotypes with age and the presence of CMV revealed a lower abundance of V delta 2-positive and a higher amount of V delta 1-positive cells. We found higher frequencies of late-differentiated and lower frequencies of early-differentiated cells in the V delta 1+ and V delta 1-V delta 2-, but not in the V delta 2+ populations in elderly CMV-seropositive individuals confirming the association of these V delta 2-negative cells with CMV-immunosurveillance. We identified the highest V delta 1:V delta 2 ratios in the CMV-seropositive elderly. The observed increased CD4:CD8 ratios in the elderly were significantly lower in CMV-seropositive individuals, who also possessed a lower naive and a larger late-differentiated compartment of CD8+ alpha beta T-cells, reflecting the consensus in the literature. Conclusions: Our findings illustrate in detail the strong influence of CMV on the abundance and differentiation pattern of gamma delta T-cells as well as alpha beta T-cells in older and younger people. Mechanisms responsible for the phenotypic alterations in the gamma delta T-cell compartment, associated both with the presence of CMV and with age require further clarification.