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 (T-reg) 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. Design and 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 T-reg-cell numbers were detected in obese compared with nonobese study participants (P = 0.038). Circulating CD4(+)CD25(+)CD127(-)Foxp3 T-reg 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 T-reg cells were below this threshold. The T-reg 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. Conclusion: Our findings thus reveal an association between circulating T-reg cells and measures of adiposity, inflammation, and glucose intolerance. Although further prospective studies are needed, we present data suggesting that the determination of T-reg cells might be useful to identify obese subjects at increased risk of developing cardiovascular and/or metabolic complications.