title: Clonal restriction and predominance of regulatory T cells in coronary thrombi of patients with acute coronary syndromes.
abstract: OBJECTIVE
  Regulatory T cells (Treg) exert anti-inflammatory and atheroprotective effects in experimental atherosclerosis. Treg can be induced against specific antigens using immunization strategies associated with clonal restriction. No data exist on Treg in combination with clonal restriction of T cells in patients with acute coronary syndromes (ACS).
  
  
  RESULTS
  Among T cell subsets characterized by flow cytometry, Treg (CD4(+) CD25(+) CD127(low)) were twice as frequent in coronary thrombi compared with peripheral blood. Treg prevailed among T cell subsets identified in coronary thrombi. To evaluate clonal restriction, genomic DNA was extracted from coronary thrombi and peripheral blood in order to evaluate T cell receptor (TCR) β chain diversity by means of Multi-N-plex PCR using a primer speciﬁc for all TCR β V gene segments and another primer speciﬁc for TCR β J gene segments. T cell receptor diversity was reduced in thrombi compared with peripheral blood (intra-individual comparisons in 16 patients) with 8 gene rearrangements in the TCR common in at least 6 out of 16 analysed coronary thrombi. Compared with age-matched healthy controls (n = 16), TCR diversity was also reduced in peripheral blood of patients with ACS; these findings were independent of peripheral T cell numbers.
  
  
  CONCLUSIONS
  We provide novel evidence for a perturbed T cell compartment characterized by clonal restriction in peripheral blood and coronary thrombi from patients with ACS. Our findings warrant further studies on Treg as novel therapeutic targets aimed at enhancing this anti-inflammatory component of adaptive immunity in human atherothrombosis.
authors.affiliation: University Heart Center, Department of Cardiology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland Cardiovascular Research, Zurich Center of Integrative Human Physiology (ZIHP), Institute of Physiology, University of Zurich, Zurich, Switzerland roland.klingenberg@usz.ch.
authors.forename: Roland
authors.initials: R
authors.lastname: Klingenberg
authors.affiliation: Regenerative Medicine Center, Department of Cardiothoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Chad E
authors.initials: CE
authors.lastname: Brokopp
authors.affiliation: ImmunID Technologies, Grenoble, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Grivès
authors.affiliation: ImmunID Technologies, Grenoble, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Courtier
authors.affiliation: University Heart Center, Department of Cardiology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Milosz
authors.initials: M
authors.lastname: Jaguszewski
authors.affiliation: ImmunID Technologies, Grenoble, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pasqual
authors.affiliation: University Heart Center, Department of Cardiology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Vlaskou Badra
authors.affiliation: University Heart Center, Department of Cardiology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Anika
authors.initials: A
authors.lastname: Lewandowski
authors.affiliation: University Heart Center, Department of Cardiology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gaemperli
authors.affiliation: Regenerative Medicine Center, Department of Cardiothoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hoerstrup
authors.affiliation: University Heart Center, Department of Cardiology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Willibald
authors.initials: W
authors.lastname: Maier
authors.affiliation: University Heart Center, Department of Cardiology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland Cardiovascular Research, Zurich Center of Integrative Human Physiology (ZIHP), Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
authors.affiliation: University Heart Center, Department of Cardiology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland Cardiovascular Research, Zurich Center of Integrative Human Physiology (ZIHP), Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.affiliation: University Heart Center, Department of Cardiology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland Cardiovascular Research, Zurich Center of Integrative Human Physiology (ZIHP), Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Matter
mesh_terms: D054058:Acute Coronary Syndrome / Q000276:immunology*; D000328:Adult; D000368:Aged; D003328:Coronary Thrombosis / Q000276:immunology*; D005434:Flow Cytometry; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000276:immunology; D008875:Middle Aged; D009203:Myocardial Infarction / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: Acute coronary syndromes; Immunity; T cells