title: The Ratio of Regulatory (FOXP3+) to Total (CD3+) T Cells Determined by Epigenetic Cell Counting and Cardiovascular Disease Risk: A Prospective Case-cohort Study in Non-diabetics.
abstract: BACKGROUND
  Experimental and clinical evidence indicate that inflammatory processes in atherogenesis and the development of cardiovascular complications are promoted by a loss of regulatory T cell (Treg)-mediated immunological tolerance to plaque antigens. Yet, the association between alterations of systemic Treg frequency and cardiovascular disease incidence remains uncertain.
  
  
  METHODS
  A nested case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg, comprising a random subcohort (n=778) and primary cases of myocardial infarction (MI, n=276) and ischemic stroke (n=151). Pre-diagnostic FOXP3+ Treg and total CD3+ T-lymphocyte (tTL) frequencies in blood were measured by epigenetic-based, quantitative real-time PCR-assisted cell counting.
  
  
  RESULTS
  Multivariate, Prentice-weighted Cox regression analyses revealed that lower Treg/tTL ratios were not associated with the risk of either MI (lowest vs. highest sex-specific quartile; hazard ratio: 0.72, 95% confidence interval: 0.46 to 1.13; Ptrend=0.51) or stroke (HR: 0.90, 95% CI: 0.51 to 1.60; Ptrend=0.78). There were no correlations of Treg/tTL ratios with C-reactive protein, HbA1c, and various lipid parameters.
  
  
  CONCLUSIONS
  Among middle-aged adults from the general population, imbalances in the relative frequency of Tregs within the total T cell compartment do not confer an increased risk of MI or stroke.
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. Electronic address: s.barth@dkfz-heidelberg.de.
authors: Sebastian Dietmar
authors: SD
authors: Barth
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. Electronic address: r.kaaks@dkfz-heidelberg.de.
authors: Rudolf
authors: R
authors: Kaaks
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. Electronic address: t.johnson@dkfz-heidelberg.de.
authors: Theron
authors: T
authors: Johnson
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. Electronic address: v.katzke@dkfz-heidelberg.de.
authors: Verena
authors: V
authors: Katzke
authors: Ivana Türbachova Laboratory for Epigenetics, Epiontis GmbH, Rudower Chaussee 29, 12489 Berlin, Germany. Electronic address: katharina.gellhaus@epiontis.com.
authors: Katharina
authors: K
authors: Gellhaus
authors: Ivana Türbachova Laboratory for Epigenetics, Epiontis GmbH, Rudower Chaussee 29, 12489 Berlin, Germany. Electronic address: janika.schulze@epiontis.com.
authors: Janika Josephin
authors: JJ
authors: Schulze
authors: Ivana Türbachova Laboratory for Epigenetics, Epiontis GmbH, Rudower Chaussee 29, 12489 Berlin, Germany. Electronic address: sven.olek@epiontis.com.
authors: Sven
authors: S
authors: Olek
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. Electronic address: t.kuehn@dkfz-heidelberg.de.
authors: Tilman
authors: T
authors: Kühn
mesh_terms: D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D016022:Case-Control Studies; D044127:Epigenesis, Genetic; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D015994:Incidence; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011159:Population Surveillance; D016016:Proportional Hazards Models; D012306:Risk; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: Cardiovascular disease risk; Cell-type-specific epigenetic qPCR-assays; Foxp3+ regulatory T cells (Tregs); Immune tolerance; Prospective study