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CMV-independent increase in CD27−CD28+ CD8+ EMRA T cells is inversely related to mortality in octogenarians

Lookup NU author(s): Dr Carmen Martin-Ruiz, Professor Thomas von Zglinicki, Dr Gavin Richardson, Lilia Draganova, Dr Rachael Redgrave, Dr Joanna Collerton, Professor Helen Arthur, Professor Bernard Keavney, Professor Ioakim Spyridopoulos

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Cytomegalovirus (CMV) seropositivity in adults has been linked to increased cardiovascular disease burden. Phenotypically, CMV infection leads to an inflated CD8 T-lymphocyte compartment. We employed a 8-colour flow cytometric protocol to analyse circulating T cells in 597 octogenarians from the same birth cohort together with NT-proBNP measurements and followed all participants over 7 years. We found that, independent of CMV serostatus, a high number of CD27−CD28+ CD8 EMRA T-lymphocytes (TEMRA) protected from all-cause death after adjusting for known risk factors, such as heart failure, frailty or cancer (Hazard ratio 0.66 for highest vs lowest tertile; confidence interval 0.51–0.86). In addition, CD27−CD28+ CD8 EMRA T-lymphocytes protected from both, non-cardiovascular (hazard ratio 0.59) and cardiovascular death (hazard ratio 0.65). In aged mice treated with the senolytic navitoclax, in which we have previously shown a rejuvenated cardiac phenotype, CD8 effector memory cells are decreased, further indicating that alterations in T cell subpopulations are associated with cardiovascular ageing. Future studies are required to show whether targeting immunosenescence will lead to enhanced life- or healthspan.


Publication metadata

Author(s): Martin-Ruiz C, Hoffmann J, Shmeleva E, von Zglinicki T, Richardson G, Draganova L, Redgrave R, Collerton J, Arthur H, Keavney B, Spyridopoulos I

Publication type: Article

Publication status: Published

Journal: npj Aging and Mechanisms of Disease

Year: 2020

Volume: 6

Issue: 3

Online publication date: 21/02/2020

Acceptance date: 02/01/2020

Date deposited: 21/01/2020

ISSN (electronic): 2056-3973

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41514-019-0041-y

DOI: 10.1038/s41514-019-0041-y


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