Szodoray P, Papp G, Horvath I F, Barath S, Sipka S, Nakken B, Zeher M
Division of Clinical Immunology, 3rd Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Clin Exp Immunol. 2009 Sep;157(3):343-9. doi: 10.1111/j.1365-2249.2009.03966.x.
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.
本研究的目的是描述原发性干燥综合征(pSS)中具有调节特性的细胞亚群,并将这些细胞群体与临床症状相关联。在32名接受调查的患者中,23名有腺外表现(EGM),而9名仅有腺体症状。20名健康个体作为对照。通过流式细胞术测定自然杀伤(NK)细胞、自然杀伤T细胞(NK T)、产生白细胞介素(IL)-10的1型调节性T细胞(Tr1)和CD4(+)CD25(+)调节性T细胞(T(reg))的百分比,并通过酶联免疫吸附测定(ELISA)评估血清中IL-4、IL-6、IL-10、肿瘤坏死因子(TNF)-α和干扰素(IFN)-γ的细胞因子水平。进行功能测试以评估患者和对照中T(reg)细胞的抑制特性。pSS患者外周血NK、NK T和Tr1细胞百分比升高,而与对照相比,患者中CD4(+)CD25(+) T(reg)细胞频率降低。在pSS中,与仅有干燥症状的患者相比,有EGM的患者中NK T、Tr1和CD4(+)CD25(+) T(reg)细胞百分比升高。CD4(+)CD25(+) T(reg)细胞百分比与唾液流量测定值呈负相关。体外功能测定表明,与对照相比,患者中CD4(+)CD25(+) T(reg)细胞的抑制活性较低。与对照相比,患者血清IL-6和TNF-α水平升高,而IL-10降低。IL-10水平与Tr1细胞百分比之间呈负相关。pSS中所研究的调节细胞亚群的变化可能有助于疾病的发生和发展。