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- Title
Morbidly Obese Human Subjects Have Increased Peripheral Blood CD4<sup>+</sup> T Cells With Skewing Toward a Treg- and Th2-Dominated Phenotype.
- Authors
van der Weerd, Kim; Dik, Willem A.; Schrijver, Benjamin; Schweitzer, Dave H.; Langerak, Anton W.; Drexhage, Hemmo A.; Kiewiet, Rosalie M.; van Aken, Maarten O.; van Huisstede, Astrid; van Dongen, Jacques J. M.; van der Lelij, Aart-Jan; Staal, Frank J. T.; van Hagen, P. Martin
- Abstract
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+ 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.
- Subjects
OBESITY; T cells; FLOW cytometry; CYTOLOGICAL techniques; CELL proliferation; CYTOKINES
- Publication
Diabetes, 2012, Vol 61, Issue 2, p401
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db11-1065