TY - JOUR
T1 - Age-associated alterations in γδ T-cells are present predominantly in individuals infected with Cytomegalovirus
AU - Wistuba-Hamprecht, Kilian
AU - Frasca, Daniela
AU - Blomberg, Bonnie
AU - Pawelec, Graham
AU - Derhovanessian, Evelyna
N1 - Funding Information:
We would like to thank Prof. Klaus Hamprecht and Ms Wioleta Kapis (Department of Medical Virology, University Clinic Tübingen) for performing the CMV-serology; Karin Hähnel for assistance in processing the samples and Lilly Oettinger for antibody titration and flow cytometry quality control. This work was supported by the German Research Foundation [DFG-PA 361/14-1], the German Federal Ministry of Education and Research (BMBF) under grant numbers 0315890F, “Gerontoshield” and 16SV5536K, “BASE-II”, the European Commission [FP7 259679 “IDEAL”] and by NIH grant AG-32576 (BBB). Responsibility for the contents of this publication lies with the authors. The funding sources were not involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
PY - 2013/7/3
Y1 - 2013/7/3
N2 - 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.
AB - 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.
KW - γδ T-cells
KW - CMV
KW - Differentiation phenotype
KW - Human ageing
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U2 - 10.1186/1742-4933-10-26
DO - 10.1186/1742-4933-10-26
M3 - Article
C2 - 23822093
AN - SCOPUS:84879807111
VL - 10
JO - Immunity and Ageing
JF - Immunity and Ageing
SN - 1742-4933
IS - 1
M1 - 26
ER -