title: 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.
abstract: 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 naïve T-cells and increased memory T-cells, potentially associated with higher morbidity and mortality. The composition of both major compartments, γδ as well as αβ T-cells, is altered by age and CMV, but detailed knowledge of changes to the γδ 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 γδ and αβ T-cells. Correlation of frequencies and absolute counts of the identified phenotypes with age and the presence of CMV revealed a lower abundance of Vδ2-positive and a higher amount of Vδ1-positive cells. We found higher frequencies of late-differentiated and lower frequencies of early-differentiated cells in the Vδ1+ and Vδ1-Vδ2-, but not in the Vδ2+ populations in elderly CMV-seropositive individuals confirming the association of these Vδ2-negative cells with CMV-immunosurveillance. We identified the highest Vδ1:Vδ2 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 naïve and a larger late-differentiated compartment of CD8+ αβ 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 γδ T-cells as well as αβ T-cells in older and younger people. Mechanisms responsible for the phenotypic alterations in the γδ T-cell compartment, associated both with the presence of CMV and with age require further clarification.
authors.affiliation: Department of Internal Medicine II, University Medical Center, Waldhörnlestr. 22, Tübingen, 72072 Germany ; Department of Dermatology, University Medical Center, Tübingen, Germany.
authors.forename: Kilian
authors.initials: K
authors.lastname: Wistuba-Hamprecht
authors.affiliation: Department of Internal Medicine II, University Medical Center, Waldhörnlestr. 22, Tübingen, 72072 Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Haehnel
authors.affiliation: Department of Internal Medicine II, University Medical Center, Waldhörnlestr. 22, Tübingen, 72072 Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Janssen
authors.affiliation: Research Group on Geriatrics, Charité - Universitaetsmedizin, Berlin, Germany ; Institute of Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ilja
authors.initials: I
authors.lastname: Demuth
authors.affiliation: Department of Internal Medicine II, University Medical Center, Waldhörnlestr. 22, Tübingen, 72072 Germany ; The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
keywords: Aging; CMV; Differentiation Phenotypes; Flow Cytometry; Senescence; αβ T-cells; γδ T-cells