title: Circulating regulatory T cells are reduced in obesity and may identify subjects at increased metabolic and cardiovascular risk.
abstract: OBJECTIVE
  Reduced numbers of regulatory T (Treg ) cells have been observed in visceral adipose tissue of obese mice and humans. However, it is unknown whether human obesity affects circulating Treg cells and whether their number is associated with markers of systemic inflammation or glucose intolerance.
  
  
  METHODS
  Peripheral blood mononuclear cells were isolated from venous blood of obese (BMI ≥ 27 kg/m(2) ; n = 30) and nonobese (BMI ≥ 27 kg/m(2) ; n = 13) individuals and analyzed using flow cytometry for the expression of CD4, CD25, and Foxp3.
  
  
  RESULTS
  Reduced circulating Treg -cell numbers were detected in obese compared with nonobese study participants (P = 0.038). Circulating CD4(+) CD25(+) CD127(-) Foxp3 Treg cells inversely correlated with body weight (P = 0.009), BMI (P = 0.004) and plasma leptin levels (P = 0.004) and were reduced in subjects with hsCRP ≥ 3.0 mg/L (P = 0.034) or HbA1c ≥ 5.5% (P < 0.005). Receiver operating characteristic curve analysis revealed a cutoff of circulating Treg cells < 1.06% to be predictive for hsCRP levels ≥ 3.0 mg/L, and logistic regression showed that the risk of having hsCRP levels ≥ 3.0 mg/L was increased 9.6-fold (P = 0.008), if Treg cells were below this threshold. The Treg cutoff for HbA1c levels ≥ 5.5% was 0.73%, and this cutoff also predicted an increased risk of having elevated levels of both hsCRP and HbA1c, if only obese subjects were examined.
  
  
  CONCLUSIONS
  Our findings thus reveal an association between circulating Treg cells and measures of adiposity, inflammation, and glucose intolerance. Although further prospective studies are needed, we present data suggesting that the determination of Treg cells might be useful to identify obese subjects at increased risk of developing cardiovascular and/or metabolic complications.
authors.affiliation: Department of Cardiology and Pulmonary Medicine, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Nana-Maria
authors.initials: NM
authors.lastname: Wagner
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brandhorst
authors.forename: Frauke
authors.initials: F
authors.lastname: Czepluch
authors.forename: Mareike
authors.initials: M
authors.lastname: Lankeit
authors.forename: Christoph
authors.initials: C
authors.lastname: Eberle
authors.forename: Sebastian
authors.initials: S
authors.lastname: Herzberg
authors.forename: Vivien
authors.initials: V
authors.lastname: Faustin
authors.forename: Joachim
authors.initials: J
authors.lastname: Riggert
authors.forename: Michael
authors.initials: M
authors.lastname: Oellerich
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuss
authors.forename: Stavros
authors.initials: S
authors.lastname: Konstantinides
authors.forename: Katrin
authors.initials: K
authors.lastname: Schäfer
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000097:blood; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D011446:Prospective Studies; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit