Expression of CD4 + CD25 + regulatory T cells in peripheral blood and salivary gland of patients with primary Sjögren's syndrome
Department of Rheumatology and Immunology, Anhui Medical University Affiliated Provincial Hospital, Hefei 230001, China. Zhonghua yi xue za zhi
Objective: To investigate the expression of CD4+ CD25+ regulatory T cells (Tregs) in the peripheral blood salivary gland of patients with primary Sjögren's syndrome (pSS). Methods: Samples of peripheral venous blood were collected from 57 newly diagnosed pSS patients, 1 male and 56 females, aged 47 (20 - 76), and 46 healthy controls. The levels of CD4+ CD25+ T regulatory cells and CD4+ CD25high T regulatory cells in the peripheral blood were measured by flow-cytometric assay. Biopsy specimens of labial gland were collected from the 57 patients and 6 healthy person or patients with labial gland cyst. Pathological examination was conducted by light microscopy. Immunohistochemistry was conducted, by using monoclonal mouse anti-human to detect the expression of CD25, CD4, CD8, and CD68. Western blotting was used to detect the levels of IgG, IgM, and IgA. The salivary flow rate was measured. Schirmer's test was used to measure the tear flow rate. Results: The level of CD4+ CD25+ Tregs in the blood of pSS patients was 6.9% (2.84%-13.50%), significantly lower than that of the healthy controls [10.9% (5.77%-15.3%),P < 0.001). The level of CD4+ CD25hi%g%h Tregs the blood of pSS patients was 0.6% (0.001%-1.83%), significantly lower than that of the healthy controls [1.1% (0.13%-2.45%), P<0.001]. Immunohistochemistry showed that most of the infiltrating lymphocytes in the labial gland of the pSS patients were CD4+ T cells, and there was no CD25+ T cell in both groups. The numbers of peripheral CD4+ CD25+ T cells and CD4+ CD25high Tregs in the pSS patients were not correlated with the tear flow rate, salivary flow rate, anti-SS-A/SS-B antibodies, and immunoglobulin level. Conclusion: The pSS patients show an absence of CD4+ CD25+ T cell in the labial gland of pSS patients, and reduction of the numbers of CD4+ CD25+ and CD4+ CD25high Tregs in the peripheral blood, which suggests that Tregs play an important role in the pathogenesis of salivary gland destruction in SS.
Available from: Gabor Papp
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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.
Available from: Cumhur İbrahim Başsorgun
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ABSTRACT: This study was designed to investigate whether Foxp3( +) regulatory T (Treg) cells play a role in the histopathologic changes of primary Sjögren's Syndrome (pSS) and to evaluate other factors possibly associated with Foxp3(+) Treg cells in pSS patients. The number of FoxP3-expressing T cells in peripheral blood (PB) of 39 patients with pSS, 40 patients with rheumatoid arthritis (RA), and 28 healthy controls was measured by flow-cytometer analysis. FoxP3-expressing CD4(+)CD25(+) Treg cells were analyzed in minor salivary gland (SG) tissues of 39 pSS patients. Histopathologic changes were examined by light microscopy according to Chisholm's classification. Immunohistochemistry and immunofluorescence were performed to assess the Foxp3(+) Treg in SG biopsy specim-ens. The numbers of CD4(+) T cells and FoxP3-expressing CD4(+) T cells in PB were similar in all groups. Expression of CD25 on CD4(+) T cells in PB of patients with pSS and RA was significantly higher than in healthy controls, especially for RA patients. Immunohistochemistry and immunofluorescence showed that FoxP3(+) Treg were enriched in the SGs of pSS patients, with a positive correlation between the increase in FoxP3(+) Treg in SG and the Chisholm score in pSS (p < 0.001, r = +0.605). The increase of FoxP3( +) Treg cells in the SGs of pSS patients, which is correlated with gland infiltration, suggests that natural regulatory T cells play an important role in the pathogenesis of pSS. Further studies are required to explore the mechanisms that mediate the relationship between Treg and the pathogenesis of pSS.
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