Morbidly Obese Human Subjects Have Increased Peripheral Blood CD4+ T Cells With Skewing Toward a Treg- and Th2-Dominated 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 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-3 (TCRB) repertoire (Gene Scan 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 CDS+ 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 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. Diabetes 61:401-408, 2012