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 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.
1Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Kim
K
van der Weerd
Willem A
WA
Dik
Benjamin
B
Schrijver
Dave H
DH
Schweitzer
Anton W
AW
Langerak
Hemmo A
HA
Drexhage
Rosalie M
RM
Kiewiet
Maarten O
MO
van Aken
Astrid
A
van Huisstede
Jacques J M
JJ
van Dongen
Aart-Jan
AJ
van der Lelij
Frank J T
FJ
Staal
P Martin
PM
van Hagen
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018946:Chemokine CCL5 / Q000097:blood; D005260:Female; D006801:Humans; D015851:Interleukin-7 / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000276:immunology*; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
C483024:CCL5 protein, human; D018946:Chemokine CCL5; D015851:Interleukin-7