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Myocardial Ischemia and Reperfusion Leads to Transient CD8 Immune Deficiency and Accelerated Immunosenescence in CMV-Seropositive Patients

Lookup NU author(s): Jedrzej Hoffmann, Dr Evgeniya Shmeleva, Dr Stephen Boag, Dr Karel Fiser, Dr Alan Bagnall, Santosh Murali, Ian Dimmick, Dr Carmen Martin-RuizORCiD, Dr Mohaned Egred, Professor Bernard Keavney, Professor Thomas von Zglinicki, Dr Rajiv Das, Dr Stephen Todryk, Professor Ioakim SpyridopoulosORCiD

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Abstract

Rationale: There is mounting evidence of a higher incidence of coronary heart disease in cytomegalovirus-seropositive individuals.Objective: The aim of this study was to investigate whether acute myocardial infarction triggers an inflammatory T-cell response that might lead to accelerated immunosenescence in cytomegalovirus-seropositive patients.Methods and Results: Thirty-four patients with acute myocardial infarction undergoing primary percutaneous coronary intervention were longitudinally studied within 3 months after reperfusion (Cohort A). In addition, 54 patients with acute myocardial infarction and chronic myocardial infarction were analyzed in a cross-sectional study (Cohort B). Cytomegalovirus-seropositive patients demonstrated a greater fall in the concentration of terminally differentiated CD8 effector memory T cells (T-EMRA) in peripheral blood during the first 30 minutes of reperfusion compared with cytomegalovirus-seronegative patients (-192 versus -63 cells/mu L; P=0.008), correlating with the expression of programmed cell death-1 before primary percutaneous coronary intervention (r=0.8; P=0.0002). A significant proportion of T-EMRA cells remained depleted for >= 3 months in cytomegalovirus-seropositive patients. Using high-throughput 13-parameter flow cytometry and human leukocyte antigen class I cytomegalovirus-specific dextramers, we confirmed an acute and persistent depletion of terminally differentiated T-EMRA and cytomegalovirus-specific CD8(+) cells in cytomegalovirus-seropositive patients. Long-term reconstitution of the T-EMRA pool in chronic cytomegalovirus-seropositive postmyocardial infarction patients was associated with signs of terminal differentiation including an increase in killer cell lectin-like receptor subfamily G member 1 and shorter telomere length in CD8(+) T cells (2225 versus 3397 bp; P<0.001).Conclusions: Myocardial ischemia and reperfusion in cytomegalovirus-seropositive patients undergoing primary percutaneous coronary intervention leads to acute loss of antigen-specific, terminally differentiated CD8 T cells, possibly through programmed cell death-1-dependent programmed cell death. Our results suggest that acute myocardial infarction and reperfusion accelerate immunosenescence in cytomegalovirus-seropositive patients.

Publication metadata

Author(s): Hoffmann J, Shmeleva EV, Boag SE, Fiser K, Bagnall A, Murali S, Dimmick I, Pircher H, Martin-Ruiz C, Egred M, Keavney B, von Zglinicki T, Das R, Todryk S, Spyridopoulos I

Publication type: Article

Publication status: Published

Journal: Circulation Research

Year: 2015

Volume: 116

Issue: 1

Pages: 87-98

Print publication date: 01/01/2015

Online publication date: 10/11/2014

Acceptance date: 10/11/2014

Date deposited: 01/07/2015

ISSN (print): 0009-7330

ISSN (electronic): 1524-4571

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1161/CIRCRESAHA.116.304393

DOI: 10.1161/CIRCRESAHA.116.304393

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