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

Circ Res. 2015 Jan 2;116(1):87-98. doi: 10.1161/CIRCRESAHA.116.304393. Epub 2014 Nov 10.


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<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.

Keywords: aging; cytotoxic T-lymphocytes; human cytomegalovirus; myocardial infarction; programmed cell death 1; reperfusion; telomere.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CD8 Antigens / blood*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cellular Senescence / physiology*
  • Cross-Sectional Studies
  • Cytomegalovirus / immunology
  • Cytomegalovirus / metabolism*
  • Female
  • Humans
  • Immunologic Deficiency Syndromes / blood*
  • Immunologic Deficiency Syndromes / epidemiology
  • Immunologic Deficiency Syndromes / virology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Myocardial Ischemia / blood*
  • Myocardial Ischemia / epidemiology
  • Myocardial Ischemia / virology
  • Myocardial Reperfusion / methods*


  • CD8 Antigens

Supplementary concepts

  • Immune Deficiency Disease