Morbidly obese human subjects have increased peripheral blood CD4+ T cells with skewing toward a Treg- and Th2-dominated phenotype.

Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE

Publication: Alexandria, VA : American Diabetes Association
Original Publication: [New York, American Diabetes Association]

CD4-Positive T-Lymphocytes/*immunology ; Obesity, Morbid/*immunology ; T-Lymphocytes, Regulatory/*immunology ; Th2 Cells/*immunology; Adult ; Chemokine CCL5/blood ; Female ; Humans ; Interleukin-7/blood ; Lymphocyte Activation ; Male ; Middle Aged ; 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.

Curr Opin Immunol. 2005 Oct;17(5):468-75. (PMID: 16098723)
Biochem Biophys Res Commun. 2010 Apr 9;394(3):562-8. (PMID: 20227394)
Annu Rev Immunol. 2011;29:415-45. (PMID: 21219177)
Nat Med. 2009 Aug;15(8):914-20. (PMID: 19633658)
Nat Rev Immunol. 2003 Jan;3(1):23-35. (PMID: 12511873)
Circulation. 2004 Sep 21;110(12):1564-71. (PMID: 15364812)
Biochem Biophys Res Commun. 2006 Aug 4;346(3):721-6. (PMID: 16782068)
Nature. 1990 Oct 18;347(6294):669-71. (PMID: 1699135)
Nat Rev Cardiol. 2009 Jun;6(6):399-409. (PMID: 19399028)
J Am Diet Assoc. 1999 Mar;99(3):294-9. (PMID: 10076580)
Arq Bras Endocrinol Metabol. 2009 Mar;53(2):183-9. (PMID: 19466211)
Science. 1995 Sep 22;269(5231):1727-30. (PMID: 7569902)
Nat Med. 2009 Aug;15(8):921-9. (PMID: 19633657)
Obes Surg. 2005 Nov-Dec;15(10):1463-8. (PMID: 16354528)
Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1608-14. (PMID: 19644053)
Int J Obes (Lond). 2008 Mar;32(3):451-63. (PMID: 17895881)
JAMA. 2010 Jan 20;303(3):235-41. (PMID: 20071471)
Diabetes. 2008 Jun;57(6):1470-81. (PMID: 18305141)
Biochem Biophys Res Commun. 2009 Jul 10;384(4):482-5. (PMID: 19422792)
Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):1304-10. (PMID: 18420999)
Semin Immunol. 2003 Feb;15(1):5-14. (PMID: 12495636)
J Clin Invest. 2007 Jan;117(1):175-84. (PMID: 17200717)
Metabolism. 2009 Aug;58(8):1087-95. (PMID: 19439330)
Nat Med. 2000 Sep;6(9):1036-42. (PMID: 10973325)
Trends Immunol. 2009 Jul;30(7):366-73. (PMID: 19540807)
PLoS Med. 2009 Apr 28;6(4):e1000058. (PMID: 19399161)
Eur J Endocrinol. 2009 Oct;161(4):567-73. (PMID: 19628651)
Leukemia. 2003 Dec;17(12):2257-317. (PMID: 14671650)
Clin Immunol. 2010 Jan;134(1):33-46. (PMID: 19635683)
J Leukoc Biol. 2008 Oct;84(4):882-92. (PMID: 18579754)
Metabolism. 2008 Oct;57(10):1375-9. (PMID: 18803941)
J Immunol. 2010 Aug 1;185(3):1836-45. (PMID: 20581149)
Lancet. 2005 Aug 20-26;366(9486):662-4. (PMID: 16112303)
Am J Physiol Endocrinol Metab. 2009 Jun;296(6):E1262-8. (PMID: 19240255)
J Mol Med (Berl). 2001 Nov;79(11):631-40. (PMID: 11715066)
J Pathol. 2007 Jan;211(2):144-56. (PMID: 17200946)
Clin Endocrinol (Oxf). 2001 Mar;54(3):347-54. (PMID: 11298087)
Nature. 2006 Dec 14;444(7121):840-6. (PMID: 17167471)
Curr Opin Clin Nutr Metab Care. 2010 Jul;13(4):366-70. (PMID: 20473150)
Metabolism. 2007 Jul;56(7):998-1004. (PMID: 17570264)
Circulation. 2006 Oct 31;114(18):1977-84. (PMID: 17043169)
J Clin Invest. 2005 May;115(5):1111-9. (PMID: 15864338)
Atherosclerosis. 2005 Dec;183(2):308-15. (PMID: 16285994)
Nat Immunol. 2010 Oct;11(10):889-96. (PMID: 20856220)
Curr Biol. 2010 Nov 23;20(22):R970-1. (PMID: 21093786)
Annu Rev Immunol. 2004;22:745-63. (PMID: 15032595)
Blood. 2009 Oct 29;114(18):3803-12. (PMID: 19721009)
Clin Immunol. 2009 Aug;132(2):153-65. (PMID: 19428306)
Mediators Inflamm. 2010;2010:. (PMID: 20706689)
Circulation. 2007 Feb 27;115(8):1029-38. (PMID: 17296858)
Am J Physiol Endocrinol Metab. 2007 Sep;293(3):E656-65. (PMID: 17578888)
J Clin Endocrinol Metab. 2009 Nov;94(11):4619-23. (PMID: 19837929)

0 (CCL5 protein, human)
0 (Chemokine CCL5)
0 (Interleukin-7)

Date Created: 20120110 Date Completed: 20120313 Latest Revision: 20220316

20240829

PMC3266399

10.2337/db11-1065

22228716