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

Carmen Martin-Ruiz; Jedrzej Hoffmann; Evgeniya Shmeleva; Thomas von Zglinicki; Gavin Richardson; Lilia Draganova; Rachael Redgrave; Joanna Collerton; Helen Arthur; Bernard Keavney; Ioakim Spyridopoulos

doi:10.1038/s41514-019-0041-y

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

NPJ Aging Mech Dis. 2020 Jan 21:6:3. doi: 10.1038/s41514-019-0041-y. eCollection 2020.

Authors

Carmen Martin-Ruiz^{1

2}, Jedrzej Hoffmann³, Evgeniya Shmeleva⁴, Thomas von Zglinicki^{1

5}, Gavin Richardson¹, Lilia Draganova⁶, Rachael Redgrave¹, Joanna Collerton¹, Helen Arthur¹, Bernard Keavney^{7

8}, Ioakim Spyridopoulos^{1

6}

Affiliations

¹ 1Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
² 2Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
³ 3Department of Medicine, Cardiology, Goethe University Hospital Frankfurt, Frankfurt a. M., Germany.
⁴ 4Department of Pathology, University of Cambridge, Cambridge, UK.
⁵ 5Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
⁶ 6Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
⁷ 7UK Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
⁸ 8Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

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.

Keywords: Biomarkers; Senescence.

Abstract

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