Morbidly Obese Human Subjects Have Increased Peripheral Blood CD4+ T Cells With Skewing Toward a Treg- and Th2-Dominated Phenotype
- Kim van der Weerd1,
- Willem A. Dik1,
- Benjamin Schrijver1,
- Dave H. Schweitzer2,
- Anton W. Langerak1,
- Hemmo A. Drexhage1,
- Rosalie M. Kiewiet3,
- Maarten O. van Aken4,
- Astrid van Huisstede5,
- Jacques J.M. van Dongen1,
- Aart-Jan van der Lelij6,
- Frank J.T. Staal7 and
- P. Martin van Hagen1,6⇓
- 1Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands
- 2Department of Internal Medicine, Reinier de Graaf Group of Hospitals, Delft, the Netherlands
- 3Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, the Netherlands
- 4Department of Internal Medicine, Haga Hospital, The Hague, the Netherlands
- 5Department of Pulmonology, Sint Franciscus Gasthuis, Rotterdam, the Netherlands
- 6Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
- 7Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands
- Corresponding author: P. Martin van Hagen, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-1065/-/DC1.
- Received July 29, 2011.
- Accepted November 25, 2011.
- © 2012 by the American Diabetes Association.
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