title: Regulatory/effector T-cell ratio is reduced in coronary artery disease.
abstract: BACKGROUND
  The protective function of regulatory T cells (Treg) has been identified in experimental atherosclerosis, but the contribution of Treg to the pathogenesis of human coronary artery disease (CAD) remains poorly understood. We investigated Treg and regulatory T-cell/effector T-cell (Treg/Teff) ratio in peripheral blood samples from CAD patients using a new strategy for precise identification of Treg. METHODS AND RESULTS: Peripheral blood samples were collected from 73 stable CAD patients (55 middle-aged CAD patients and 18 old CAD patients) and 64 controls (47 middle-aged controls and 17 young controls). CD3(+)CD4(+)FoxP3(+)T cells were divided into 3 fractions: CD45RA(+)FoxP3(low)resting Treg(Fr1), CD45RA(-)FoxP3(high)activated Treg(Fr2), and CD45RA(-)FoxP3(low)non-Treg(Fr3). CAD patients had lower percentages of Fr1 and Fr2 and higher percentages of Fr3 and CD45RA(-)Foxp3(-)Teff(Fr4+5) within the CD3(+)CD4(+)T-cell population compared to age-matched controls. Treg/Teff ratio (Fr1+2/Fr3+4+5) in CAD patients was also markedly lower than in controls (middle-aged control, 0.17±0.09 vs. middle-aged CAD, 0.10±0.05; P<0.001). The percentage of CD4(+)CD28(null)T cells within the CD4(+)T-cell population was negatively correlated with Treg/Teff ratio, excluding CD4(+)CD28(null)T cells <0.3% (r=-0.27, P<0.05). High-sensitivity C-reactive protein was also negatively correlated with Treg/Teff ratio (r=-0.22, P<0.05).
  
  
  CONCLUSIONS
  CAD patients had reduced Treg and Treg/Teff ratio compared to healthy controls. The present findings may be helpful when developing immunotherapy for the prevention of CAD.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine.
authors.forename: Takuo
authors.initials: T
authors.lastname: Emoto
authors.forename: Naoto
authors.initials: N
authors.lastname: Sasaki
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kasahara
authors.forename: Keiko
authors.initials: K
authors.lastname: Yodoi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Taiji
authors.initials: T
authors.lastname: Mizoguchi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology; D000787:Angina Pectoris / Q000097:blood / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D001786:Blood Glucose; D008055:Lipids