title: Low levels of circulating CD4+FoxP3+ T cells are associated with an increased risk for development of myocardial infarction but not for stroke.
abstract: OBJECTIVE
  Regulatory T cells (Tregs) protect against atherosclerosis in experimental models, but their association with cardiovascular disease in humans remains to be elucidated. The aim of the present study was to determine whether circulating Tregs predict the development of acute cardiovascular events in humans.
  
  
  RESULTS
  The study cohort consisted of a random sample of participants (n=700), aged 68 to 73 years, from the Malmö Diet and Cancer Study. Mononuclear leukocytes, stored at -140 degrees C at the baseline investigation in 1991-1994, were thawed and Tregs, defined by the expression of FoxP3 in CD4+ T cells, were analyzed by flow cytometry. There was no detectable loss of cells during storage, and the viability of thawed leukocytes was 95%. A low fraction of both CD4+FoxP3+ and CD4+CD25+FoxP3+ T cells was associated with a higher release of proinflammatory cytokines from activated mononuclear leukocytes, and this association was strongest for CD4+FoxP3+ cells. Eighty-four coronary events and 66 strokes were registered during follow-up until December 31, 2008. In a Cox proportional hazard regression model adjusting for major risk factors, low levels of baseline CD4+FoxP3+ T cells were associated with an increased risk for the development of acute coronary events but not stroke. There were no associations between CD4+CD25+FoxP3+ T cells and development of an acute coronary event or stroke.
  
  
  CONCLUSIONS
  This study provides prospective evidence for the role of Tregs in the development of myocardial infarction. The findings are in accordance with previous experimental studies and provide clinical support for a protective role of Tregs in atherosclerosis. The lack of association between Tregs and stroke may reflect the more heterogeneous cause of this disease.
authors.affiliation: Department of Clinical Sciences, Entrance 72, 60:13, Malmö University Hospital, 20502 Malmö, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Wigren
authors.forename: Harry
authors.initials: H
authors.lastname: Björkbacka
authors.forename: Linda
authors.initials: L
authors.lastname: Andersson
authors.forename: Irena
authors.initials: I
authors.lastname: Ljungcrantz
authors.forename: Gunilla Nordin
authors.initials: GN
authors.lastname: Fredrikson
authors.forename: Margaretha
authors.initials: M
authors.lastname: Persson
authors.forename: Carl
authors.initials: C
authors.lastname: Bryngelsson
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000209:etiology; D059168:Carotid Intima-Media Thickness; D015331:Cohort Studies; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006801:Humans; D009203:Myocardial Infarction / Q000209:etiology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D020521:Stroke / Q000209:etiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors