Morbidly obese human subjects have increased peripheral blood [CD4.sup.+] T cells with skewing toward a Treg- and Th2-doroinated phenotype

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 subpopulations via six-color flow cytometry, including [CD8.sup.+] and [CD4.sup.+] T cells, [CD4.sup.+] T-helper (Th) subpopulations, and natural [CD4.sup.+][CD25.sup.+][FoxP3.sup.+] T-regulatory (Treg) cells. Moreover, molecular analyses to assess thymic output, T-cell proliferation (T-cell receptor excision circle analysis), and T-cell receptor-[beta] (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.sup.+] naive, memory, natural [CD4.sup.+][CD25.sup.+][FoxP3.sup.+] Treg, and Th2 T cells, whereas [CD8.sup.+] T cells were normal. [CD4.sup.+] and [CD8.sup.+] T-cell proliferation was increased, whereas the TCRB repertoire was not significantly altered. Plasma levels of cytokines CCL5 and IL-7 were elevated. [CD4.sup.+] 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.sup.+] T cells, with skewing toward a Treg- and Th2-dominated phenotype, suggesting a more anti-inflammatory set point. Diabetes 61:401-408, 2012