类风湿关节炎患者外周血调节性t淋巴细胞亚群的研究

P N Kravchenko, G A Zhulai, A V Churov, E K Oleinik, V M Oleinik, O Yu Barysheva, N N Vezikova, I M Marusenko
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引用次数: 8

摘要

背景:类风湿关节炎(RA)是一种与T细胞介导的耐受性功能障碍相关的炎症性风湿性疾病,可导致工作人群的残疾。调节性CD4 T细胞在自身免疫调节中发挥重要作用,可抑制免疫应答。因此,这些淋巴细胞的含量及其在RA发病中的作用尚无共识。目的:通过观察RA患者外周血调节性t细胞(Treg)的膜标志物CD4、CD25、CD127和细胞内FOXP3标志物的表达情况,以及两种功能分子(CTLA-4和CCR4)在Treg细胞中的表达情况,评估Treg的含量。方法:采集RA患者(中位年龄65,5岁[54;68,3])和健康对照(中位年龄58岁[44;[66])进行分析。流式细胞术检测细胞计数及分子表达水平。结果:对36例RA患者和20例健康献血者的外周血进行了分析。与健康供者相比,RA患者中CD4 + CD25hi和CD4 + CD25hiCD127low/⁻的细胞数更高。还观察到表达FOXP3的RA CD4 + T细胞水平升高。这可能是由于CD4 + FOXP3 + CD25⁻淋巴细胞的数量增加,而RA + CD4 + FOXP3 + CD25 + Treg细胞的含量处于对照组水平。RA患者Treg细胞中功能分子CTLA-4的表达与对照组无差异,而在炎症和屏障组织部位提供淋巴细胞迁移的趋化因子受体CCR4的表达水平在RA患者中显著升高。结论:RA患者外周血中某些treg相关淋巴细胞群水平升高。在RA的自然过程中,趋化因子受体CCR4水平的改变可能表明淋巴细胞迁移增强。
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[Subpopulations of Regulatory T-lymphocytes in the Peripheral Blood of Patients with Rheumatoid Arthritis].

Background: Rheumatoid arthritis (RA) is an inflammatory rheumatic disease associated with a dysfunction of the T cell-mediated tolerance and leading to the disability of working population. The regulatory CD4' T cells play an important role in the regulation of autoimmunity and can suppress immune responses. With that, there is no consensus on the content of these lymphocytes and their role in the pathogenesis of RA. Objective: The aim of the study was to assess the content ofperipheral blood regulatory Tcells (Treg) according to the expression of membrane markers CD4, CD25, CD127 and intracellular FOXP3 marker, as well as the expression of two functional molecules (CTLA-4 and CCR4) in Treg cells of patients with RA.

Methods: Peripheral blood samples of RA patients (median age 65,5 years [54;68,3) and healthy controls (median age 58 years [44; 66]) were analyzed. Cell count and the expression level of molecules were assessed by flow cytometry.

Results: Peripheral blood samples of 36 RA patients and 20 healthy donors were analyzed. The number of the cells with Treg-associated phenotypes CD4⁺CD25hi and CD4⁺CD25hiCD127low/⁻ was higher in RA patients in comparison with healthy donors. Increased levels of RA CD4⁺ T cells expressing FOXP3 were also observed. This may be due to increasing in the number of CD4⁺FOXP3⁺CD25⁻ lymphocytes, whereas the content of RA CD4⁺FOXP3⁺CD25⁺ Treg cells was at the level of the control. The expression of the functional molecule CTLA-4 in Treg cells of patients with RA was not different from the control, while the expression level of the chemokine receptor CCR4 which provides migration of lymphocytes at sites of inflammation and barrier tissues was significantly increased in RA patients.

Conclusion: Increase in the levels of certain Treg-associated lymphocyte populations were detected in peripheral blood of RA patients. During the natural course of RA, alterations in the level of the chemokine receptor CCR4 might indicate the enhanced lymphocyte migration.

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