Cells with Regulatory Function of the Innate and Adaptive Immune System in Primary Sjögren's Syndrome

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2009 Aug 12

PMID 19664141

Citations 35

Authors

P Szodoray

G Papp

I F Horvath

S Barath

S Sipka

B Nakken

M Zeher

Affiliations

Soon will be listed here.

Abstract

The aim of the present study was to describe subsets of cells with regulatory properties in primary Sjögren's syndrome (pSS), and to correlate these cell populations with clinical symptoms. Among the 32 investigated patients, 23 had extraglandular manifestations (EGMs), while nine had only glandular symptoms. Twenty healthy individuals served as controls. The percentages of natural killer (NK), natural killer T cells (NK T), interleukin (IL)-10 producing T regulatory type 1 (Tr1) cells and CD4(+)CD25(+) regulatory T cells (T(reg)) cells were determined by flow cytometry and serum cytokine levels of IL-4, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma were evaluated by enzyme-linked immunosorbent assay (ELISA). Functional tests were carried out to assess the suppressor properties of T(reg) cells in patients and controls. Peripheral NK, NK T and Tr1 cell percentages were elevated in pSS, while CD4(+)CD25(+) T(reg) cells showed reduced frequencies in patients compared to controls. In pSS, elevated percentages of NK T, Tr1 and CD4(+)CD25(+) T(reg) cells were observed in patients with EGMs, when compared to patients with sicca symptoms only. CD4(+)CD25(+) T(reg) cell percentages showed a negative correlation with sialometry values. The in vitro functional assay demonstrated lower suppression activity of CD4(+)CD25(+) T(reg) cells in patients compared to controls. Serum IL-6 and TNF-alpha levels were elevated, while IL-10 was decreased in patients compared to controls. Negative correlation was found between IL-10 levels and the percentages of Tr1 cells. Changes in the investigated subsets of regulatory cells in pSS may contribute to the development and progression of the disease.

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References

Bettelli E, Carrier Y, Gao W, Korn T, Strom T, Oukka M . Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006; 441(7090):235-8. DOI: 10.1038/nature04753. View

Yagi H, Nomura T, Nakamura K, Yamazaki S, Kitawaki T, Hori S . Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int Immunol. 2004; 16(11):1643-56. DOI: 10.1093/intimm/dxh165. View

Li X, Li X, Qian L, Wang G, Zhang H, Zhei Z . [Expression of CD4+ CD25+ regulatory T cells in peripheral blood and salivary gland of patients with primary Sjögren's syndrome]. Zhonghua Yi Xue Za Zhi. 2007; 87(15):1034-6. View

Li X, Li X, Qian L, Wang G, Zhang H, Wang X . T regulatory cells are markedly diminished in diseased salivary glands of patients with primary Sjögren's syndrome. J Rheumatol. 2007; 34(12):2438-45. View

Goodnow C . Balancing immunity and tolerance: deleting and tuning lymphocyte repertoires. Proc Natl Acad Sci U S A. 1996; 93(6):2264-71. PMC: 39784. DOI: 10.1073/pnas.93.6.2264. View

Fehervari Z, Sakaguchi S . A paragon of self-tolerance: CD25+CD4+ regulatory T cells and the control of immune responses. Arthritis Res Ther. 2004; 6(1):19-25. PMC: 400424. DOI: 10.1186/ar1037. View

Deniz G, Erten G, Kucuksezer U, Kocacik D, Karagiannidis C, Aktas E . Regulatory NK cells suppress antigen-specific T cell responses. J Immunol. 2008; 180(2):850-7. DOI: 10.4049/jimmunol.180.2.850. View

Sprent J, Kishimoto H . The thymus and central tolerance. Philos Trans R Soc Lond B Biol Sci. 2001; 356(1409):609-16. PMC: 1088448. DOI: 10.1098/rstb.2001.0846. View

Baecher-Allan C, Brown J, Freeman G, Hafler D . CD4+CD25high regulatory cells in human peripheral blood. J Immunol. 2001; 167(3):1245-53. DOI: 10.4049/jimmunol.167.3.1245. View

10.

Green M, Kennell A, Larche M, Seifert M, Isenberg D, Salaman M . Natural killer T cells in families of patients with systemic lupus erythematosus: their possible role in regulation of IGG production. Arthritis Rheum. 2006; 56(1):303-10. DOI: 10.1002/art.22326. View

11.

Li X, Xiao B, Xi J, Lu C, Lu J . Decrease of CD4(+)CD25(high)Foxp3(+) regulatory T cells and elevation of CD19(+)BAFF-R(+) B cells and soluble ICAM-1 in myasthenia gravis. Clin Immunol. 2007; 126(2):180-8. DOI: 10.1016/j.clim.2007.10.001. View

12.

Hassan A, Gunnarsson I, Karlsson G, Klareskog L, Forslid J, Lundberg I . Longitudinal study of interleukin-10, tumor necrosis factor-alpha, anti-U1-snRNP antibody levels and disease activity in patients with mixed connective tissue disease. Scand J Rheumatol. 2001; 30(5):282-9. DOI: 10.1080/030097401753180363. View

13.

Novak J, Griseri T, Beaudoin L, Lehuen A . Regulation of type 1 diabetes by NKT cells. Int Rev Immunol. 2007; 26(1-2):49-72. DOI: 10.1080/08830180601070229. View

14.

Liu M, Lin L, Weng C, Weng M . Decreased CD4+CD25+bright T cells in peripheral blood of patients with primary Sjogren's syndrome. Lupus. 2007; 17(1):34-9. DOI: 10.1177/0961203307085248. View

15.

Jahng A, Maricic I, Pedersen B, Burdin N, Naidenko O, Kronenberg M . Activation of natural killer T cells potentiates or prevents experimental autoimmune encephalomyelitis. J Exp Med. 2001; 194(12):1789-99. PMC: 2193586. DOI: 10.1084/jem.194.12.1789. View

16.

Balandina A, Lecart S, Dartevelle P, Saoudi A, Berrih-Aknin S . Functional defect of regulatory CD4(+)CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis. Blood. 2004; 105(2):735-41. PMC: 1847365. DOI: 10.1182/blood-2003-11-3900. View

17.

Christodoulou M, Kapsogeorgou E, Moutsopoulos N, Moutsopoulos H . Foxp3+ T-regulatory cells in Sjogren's syndrome: correlation with the grade of the autoimmune lesion and certain adverse prognostic factors. Am J Pathol. 2008; 173(5):1389-96. PMC: 2570129. DOI: 10.2353/ajpath.2008.080246. View

18.

Bendelac A, Savage P, Teyton L . The biology of NKT cells. Annu Rev Immunol. 2006; 25:297-336. DOI: 10.1146/annurev.immunol.25.022106.141711. View

19.

Pasare C, Medzhitov R . Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science. 2003; 299(5609):1033-6. DOI: 10.1126/science.1078231. View

20.

Korn T, Reddy J, Gao W, Bettelli E, Awasthi A, Petersen T . Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med. 2007; 13(4):423-31. PMC: 3427780. DOI: 10.1038/nm1564. View