趋化因子受体CCR5及其配体在类风湿关节炎患者滑液及滑膜中的表达

目的查明趋化因子C-C亚族受体5(CCR5)及其配体在外周血、关节滑膜和滑液的表达及分布,探讨Th1细胞选择性聚集于类风湿关节炎(RA)患者关节中的机制.方法采用两色和三色免疫荧光标记、流式细胞术及激光扫描共聚焦显微技术,对15例RA患者外周血、关节液及滑膜中Th细胞亚群,以及趋化因子受体CCR5和CXCR3的表达细胞,和C-C亚族趋化因子巨噬细胞炎性蛋白(MIP)-1β的产生细胞,进行了测定和分析比较.结果(1)RA患者关节滑液细胞内细胞因子分泌模式明显向Th1偏移,Th1样细胞在关节内占优势.(2)RA患者滑液中T细胞受体CCR5的表达率为52%±8%,CXCR3的表达率为61%±12%,与自身及正常人(外周血单个核细胞)比较明显升高(P＜0.01).(3)RA患者滑膜组织中大量浸润的T细胞(尤其是CD4+细胞)、单核/巨噬细胞(Mo/Mac)、B细胞多表达CCR5的配体MIP-1β.结论RA患者的关节内,T细胞、B细胞、Mo-Mac产生MIP-1β、RANTERS等趋化因子,能趋化表达CCR5、CXCR3的Th1细胞选择性进入关节组织,导致Th1/Th2细胞失衡.

Expression of CCR5 and its ligand in joint fluid and synovium of patients with rheuatoid arthritis

Objective To investigate the expression and distribution of C C chemokine recepter 5 (CCR5) and its ligand in peripheral blood, synovium, and synovial fluid so as to study the mechanism of selective accumulation of Th1 cells in rheumatoid joints. Methods Synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) were isolated from 15 patients with active rheumatoid arthritis (RA). The expressions of intracellular cytokines, CCR5 and CXCR3 on cytomembraine of SFMCs and PBMCs, and MIP 1 immunofluorescence labelling, and flow cytometry. Results (1) The selective pattern of intracellular cytokines in SFMCs was drifted towards Th1 subset. (2) The expression rate of CCR5 was 52% Y 8%, the expression rate of CXCR3 was 61% Y 12% in synovial fluid, significantly higher than those of PBMCs. (3) In RA tissues, most of the infiltrating T cells (especially CD4 T cells), monocyres/microphages, and B cells expressed macrophage inflammatory protein, ligand of CCR5. Conclusion Infiltrating T cells (especially CD4 T((MIP) 1 cells), monocyres/microphages, and B cells in the synovium of inflammatory, RANTES, and other cytokines which cause the accumulation of CCR5 Th1 cells.