Morbidly Obese Human Subjects Have Increased Peripheral Blood CD4+ T Cells With Skewing Toward a Treg- and Th2-Dominated Phenotype

  1. P. Martin van Hagen1,6
  1. 1Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands
  2. 2Department of Internal Medicine, Reinier de Graaf Group of Hospitals, Delft, the Netherlands
  3. 3Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, the Netherlands
  4. 4Department of Internal Medicine, Haga Hospital, The Hague, the Netherlands
  5. 5Department of Pulmonology, Sint Franciscus Gasthuis, Rotterdam, the Netherlands
  6. 6Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
  7. 7Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands
  1. Corresponding author: P. Martin van Hagen, p.m.vanhagen{at}erasmusmc.nl.

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.

Footnotes

  • Received July 29, 2011.
  • Accepted November 25, 2011.

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