title: Elevated pro-inflammatory CD4+CD28- lymphocytes and stroke recurrence and death.
abstract: OBJECTIVE
  To determine if the CD4+CD28- T-cell subset is expanded in patients with recurrent stroke or death after acute ischemic stroke. This subset of the peripheral blood T-cell lymphocyte population has a strong pro-inflammatory and tissue-damaging potential.
  
  
  METHODS
  Consecutive patients within the first 48 hours of ischemic stroke were prospectively studied. Peripheral blood CD4+CD28- cells were quantified by flow cytometry. The study endpoint was recurrent stroke or death from any cause during 1 year of follow-up.
  
  
  RESULTS
  One hundred six patients (mean age 75.0 +/- 13.5 years; 50 women) were studied. The median CD4+CD28- cell count was 4.5% (range 0.2 to 72.2%). Twenty-seven endpoints (10 recurrent strokes and 17 deaths) occurred during follow-up. Stroke recurrence/death rates were significantly associated with increasing CD4+CD28- counts, rising from 14.2% in patients with CD4+CD28- levels of <1.0 to 48.1% for those with CD4+CD28- counts of >8.0% (p = 0.003, Cochran linear test of trend). Higher CD4+CD28- counts were also present in patients with a history of prior stroke (p = 0.03). After adjustment for age, admission NIH Stroke Scale score, prior stroke, and atrial fibrillation, CD4+CD28- counts of >8.0% were associated with a cumulative hazard ratio of 5.81 (95% CI: 1.58 to 21.32) for stroke recurrence or death.
  
  
  CONCLUSIONS
  Rising counts of circulating CD4+CD28- cells are associated with an increasing risk of stroke recurrence and death, in addition to an observed association with prior stroke. Expansion of this T-cell subset presumably represents a biomarker and possibly a contributory pathogenic mechanism of recurrent stroke and death after ischemic stroke.
authors.affiliation: Stroke Branch, National Institute of Neurologic Disorders and Stroke, NIH, 10 Center Dr., Bethesda, MD 20892-1294, USA.
authors.forename: Z G
authors.initials: ZG
authors.lastname: Nadareishvili
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: V
authors.initials: V
authors.lastname: Wright
authors.forename: D
authors.initials: D
authors.lastname: Maric
authors.forename: S
authors.initials: S
authors.lastname: Warach
authors.forename: J M
authors.initials: JM
authors.lastname: Hallenbeck
authors.forename: J
authors.initials: J
authors.lastname: Dambrosia
authors.forename: J L
authors.initials: JL
authors.lastname: Barker
authors.forename: A E
authors.initials: AE
authors.lastname: Baird
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000150:complications; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000276:immunology* / Q000401:mortality; D018106:CD28 Antigens / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004660:Encephalitis / Q000276:immunology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000276:immunology* / Q000401:mortality; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D015415:Biomarkers; D018106:CD28 Antigens