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.
|CD4+ T lymphocyte, CD8+ T lymphocyte, T lymphocyte subpopulation, Th1 cell, Th17 cell, Th2 cell, adipose tissue, article, cell compartmentalization, clinical article, controlled study, flow cytometry, homeostasis, human, human cell, insulin blood level, lean body weight, lymphocyte proliferation, memory cell, morbid obesity, peripheral lymphocyte, phenotype, priority journal, regulatory T lymphocyte, thymus|
|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