Morbidly obese human subjects have increased peripheral blood CD4 + T cells with skewing toward a Treg- and Th2-dominated phenotype
Diabetes , Volume 61 - Issue 2 p. 401- 408
Obesity is associated with local T-cell abnormalities in adipose tissue. Systemic obesity-related abnormalities in the peripheral blood T-cell compartment are not well defined. In this study, we investigated the peripheral blood T-cell compartment of morbidly obese and lean subjects. We determined all major T-cell sub-populations via six-color flow cytometry, including CD8+and CD4+T cells, CD4+T-helper (Th) subpopulations, and natural CD4+CD25+FoxP3+T-regulatory (Treg) cells. Moreover, molecular analyses to assess thymic output, T-cell proliferation (T-cell receptor excision circle analysis), and T-cell receptor-β (TCRB) repertoire (GeneScan analysis) were performed. In addition, we determined plasma levels of proinflammatory cytokines and cytokines associated with Th subpopulations and T-cell proliferation. Morbidly obese subjects had a selective increase in peripheral blood CD4+naive, memory, natural CD4+CD25+FoxP3+Treg, and Th2 T cells, whereas CD8+T cells were normal. CD4+and CD8+T-cell proliferation was increased, whereas the TCRB repertoire was not significantly altered. Plasma levels of cytokines CCL5 and IL-7 were elevated. CD4+T-cell numbers correlated positively with fasting insulin levels. The peripheral blood T-cell compartment of morbidly obese subjects is characterized by increased homeostatic T-cell proliferation to which cytokines IL-7 and CCL5, among others, might contribute. This is associated with increased CD4+T cells, with skewing toward a Treg- and Th2-dominated phenotype, suggesting a more anti-inflammatory set point.
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|Organisation||Erasmus MC: University Medical Center Rotterdam|
van der Weerd, K, Dik, W.A, Schrijver, B, Schweitzer, D.H, Langerak, A.W, Drexhage, H.A, … van Hagen, P.M. (2012). Morbidly obese human subjects have increased peripheral blood CD4 + T cells with skewing toward a Treg- and Th2-dominated phenotype. Diabetes, 61(2), 401–408. doi:10.2337/db11-1065