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T Regulatory Cells Are Markedly Diminished in Diseased Salivary Glands of Patients with Primary Sjögren's Syndrome
XIAOMEI LI, XIANGPEI LI, LONG QIAN, GUOSHENG WANG, HONG ZHANG, XIAOQIU WANG, KE CHEN, ZHIMIN ZHAI, QING LI, YIPING WANG, and DAVID C.H. HARRIS
ABSTRACT. Methods. Levels of CD4+CD25+high T cells of the peripheral blood of 52 patients with pSS were measured by flow-cytometric assay. Lower lip salivary gland biopsies were examined by immunohistochemistry, using monoclonal mouse anti-human antibodies [CD25, CD4, CD8, CD68, forkhead transcription factor (Foxp3)] in 30 patients with pSS. Using real-time polymerase chain reaction, Foxp3 messenger RNA expression was assessed in the salivary glands and CD4+ T cells from peripheral blood. Results. Many inflammatory cells, predominantly CD4+ and CD8+ T cells and macrophages, were found in salivary glands of patients with SS, but CD4+CD25+ Treg numbers and Foxp3 expression were markedly reduced in those biopsy samples. Levels of CD4+CD25+high T cells and Foxp3 expression in peripheral blood of patients with pSS were significantly lower than in healthy controls. However, the inhibitory function of CD4+CD25+ T cells in pSS was unchanged compared to that of controls. Peripheral CD4+CD25+high T cell numbers in pSS did not correlate with Schirmer's test and salivary flow rate, or with the presence or absence of anti-SSA/SSB antibodies and immunoglobulin level. Conclusion. The remarkable reduction of Treg numbers in salivary glands and reduction of CD4+CD25+high T cells in peripheral blood suggests a possible role for absence of Treg in the pathogenesis of salivary gland destruction in pSS. (First Release Nov 15 2007; J Rheumatol 2007;34:2438-45) Key Indexing Terms:
PRIMARY SJÖGREN'S SYNDROME From the Department of Rheumatology and Immunology, Anhui Medical University Affiliated Provincial Hospital, Hefei, Anhui Province, China; and Centres for Transplantation and Renal Research, the University of Sydney at Westmead Millennium Institute, Sydney, Australia. Supported by Anhui Provincial Hospital Research Foundation (2005YZ15) and the Clinical Key Project of Anhui Province (05A008 and 06B024). X. Li, MD, Professor, Department of Rheumatology and Immunology, Anhui Medical University Affiliated Provincial Hospital and Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute; X. Li, MD, Professor; L. Qian, MD, Associate Professor; G. Wang, MD, Associate Professor; H. Zhang, Technician, Department of Rheumatology and Immunology; X. Wang, Technician; K. Chen, MD, Professor, Department of Pathology; Z. Zhai, PhD, Professor; Q. Li, BD, Technician, Centre for Laboratory, Anhui Medical University Affiliated Provincial Hospital; Y. Wang, PhD, Senior Researcher; D.C.H. Harris, MD, BS, FRACP, Professor, Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute. Address reprint requests to Prof. Xiaomei Li, Department of Rheumatology and Immunology, Anhui Medical University Affiliated Provincial Hospital, Hefei, Anhui, P.R. China. E-mail: Lixiaomei1@medmail.com.cn Accepted for publication August 9, 2007. |
