Myocardial ischemia and reperfusion leads to transient CD8 immune deficiency and accelerated immunosenescence in CMV-seropositive patients.

Jedrzej Hoffmann, Evgeniya V Shmeleva, Stephen E Boag, Karel Fiser, Alan Bagnall, Santosh Murali, Ian Dimmick, Hanspeter Pircher, Carmen Martin-Ruiz, Mohaned Egred, Bernard Keavney, Thomas von Zglinicki, Rajiv Das, Stephen Todryk, Ioakim Spyridopoulos

    Research output: Contribution to journalArticlepeer-review

    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 (TEMRA) in peripheral blood during the first 30 minutes of reperfusion compared with cytomegalovirus-seronegative patients (-192 versus -63 cells/μL; 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 TEMRA 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 TEMRA and cytomegalovirus-specific CD8(+) cells in cytomegalovirus-seropositive patients. Long-term reconstitution of the TEMRA 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
    Original languageEnglish
    JournalCirculation research
    Volume116
    Issue number1
    DOIs
    Publication statusPublished - 2 Jan 2015

    Keywords

    • aging
    • cytotoxic T-lymphocytes
    • human cytomegalovirus
    • myocardial infarction
    • programmed cell death 1
    • reperfusion
    • telomere

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