title: Functional and homeostatic defects of regulatory T cells in patients with coronary artery disease.
abstract: OBJECTIVE
  Regulatory T cells (Tregs) are considered atheroprotective, and low levels have been associated with the acute coronary syndrome (ACS), particularly non-ST elevation (NSTE)-ACS. However, the functional properties as well as homeostasis of Tregs are mainly unknown in coronary artery disease (CAD). Here, we investigated the composition and functional properties of naïve (n) and memory (m)Tregs in patients with NSTE-ACS and in patients 6-12 months post-ACS.
  
  
  METHODS
  Based on the expression of CD25, FOXP3, CD127, CD45RA, CD39 and CTLA-4, Treg subsets were defined by flow cytometry in whole blood or isolated CD4(+) T cells. The functional properties of nTregs and mTregs were examined in terms of proliferative capacity and modulation of cytokine secretion. To understand the potential consequences of Treg defects, we also investigated correlations with lipopolysaccharide (LPS)-induced cytokine secretion and ultrasound-defined carotid atherosclerosis.
  
  
  RESULTS
  Both NSTE-ACS and post-ACS patients exhibited reduced levels of nTregs (P < 0.001) compared with healthy control subjects, but without compensatory increases in mTregs. Both nTregs and mTregs from patients showed significantly lower replicative rates and impaired capacity to modulate T-cell proliferation and secretion of interferon-gamma and IL-10. The Treg defect was also associated with LPS-induced cytokine secretion and increased burden of carotid atherosclerosis.
  
  
  CONCLUSIONS
  Our results demonstrate a functional and homeostatic Treg defect in patients with NSTE-ACS and also in stabilized patients 6-12 months after ACS. Moreover, this defect was associated with a subclinical proinflammatory and atherogenic state. We believe that the failure to preserve Treg function and homeostasis reflects a need for immune-restoring strategies in CAD.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Hasib
authors.affiliation: Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: A K
authors.initials: AK
authors.lastname: Lundberg
authors.affiliation: Department of Clinical Physiology, Linköping University, Linköping, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Zachrisson
authors.affiliation: Division of Clinical Immunology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Ernerudh
authors.affiliation: Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Jonasson
mesh_terms: D000368:Aged; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D003324:Coronary Artery Disease / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D006706:Homeostasis; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D014463:Ultrasonography
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger
keywords: acute coronary syndrome; coronary artery disease; immune homeostasis; inflammation; regulatory T cell