title: T lymphocytes and fractalkine contribute to myocardial ischemia/reperfusion injury in patients.
abstract: BACKGROUND
  Lymphocytes contribute to ischemia/reperfusion (I/R) injury in several organ systems, but their relevance in ST elevation myocardial infarction (STEMI) is unknown. Our goal was to characterize lymphocyte dynamics in individuals after primary percutaneous coronary intervention (PPCI), assess the prognostic relevance of these cells, and explore mechanisms of lymphocyte-associated injury.
  
  
  METHODS
  Lymphocyte counts were retrospectively analyzed in 1,377 STEMI patients, and the prognostic relevance of post-PPCI lymphopenia was assessed by Cox proportional hazards regression. Blood from 59 prospectively recruited STEMI patients undergoing PPCI was sampled, and leukocyte subpopulations were quantified. Microvascular obstruction (MVO), a component of I/R injury, was assessed using MRI.
  
  
  RESULTS
  In the retrospective cohort, lymphopenia was associated with a lower rate of survival at 3 years (82.8% vs. 96.3%, lowest vs. highest tertile; hazard ratio 2.42). In the prospective cohort, lymphocyte counts fell 90 minutes after reperfusion, primarily due to loss of T cells. CD8+ T cells decreased more than CD4+ T cells, and effector subsets exhibited the largest decline. The early decrease in effector T cell levels was greater in individuals that developed substantial MVO. The drop in T cell subsets correlated with expression of the fractalkine receptor CX3CR1 (r2 = 0.99, P = 0.006). Serum fractalkine concentration peaked at 90 minutes after reperfusion, coinciding with the T cell count nadir.
  
  
  CONCLUSIONS
  Lymphopenia following PPCI is associated with poor prognosis. Our data suggest that fractalkine contributes to lymphocyte shifts, which may influence development of MVO through the action of effector T cells.
  
  
  BACKGROUND
  Not applicable.
  
  
  BACKGROUND
  British Heart Foundation (FS/12/31/29533) and National Institute of Health Research (NIHR) Newcastle Biomedical Research Centre.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Boag
authors.forename: Rajiv
authors.initials: R
authors.lastname: Das
authors.forename: Evgeniya V
authors.initials: EV
authors.lastname: Shmeleva
authors.forename: Alan
authors.initials: A
authors.lastname: Bagnall
authors.forename: Mohaned
authors.initials: M
authors.lastname: Egred
authors.forename: Nicholas
authors.initials: N
authors.lastname: Howard
authors.forename: Karim
authors.initials: K
authors.lastname: Bennaceur
authors.forename: Azfar
authors.initials: A
authors.lastname: Zaman
authors.forename: Bernard
authors.initials: B
authors.lastname: Keavney
authors.forename: Ioakim
authors.initials: I
authors.lastname: Spyridopoulos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D054428:Chemokine CX3CL1 / Q000097:blood*; D005260:Female; D006801:Humans; D008231:Lymphopenia / Q000097:blood / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications / Q000401:mortality; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000150:complications / Q000401:mortality; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1