Expression of functional B7 and CTLA4 on rheumatoid synovial T cells.
Expression of functional B7 and CTLA4 on rheumatoid synovial T cells.
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DOI：
10.4049/jimmunol.153.3.1378
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发表时间：
1994-08
影响因子：
4.4
通讯作者：
J. Verwilghen;R. Lovis;M. Boer;P. Linsley;G. Haines;A. Koch;R. Pope
中科院分区：
文献类型：
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作者：
J. Verwilghen;R. Lovis;M. Boer;P. Linsley;G. Haines;A. Koch;R. Pope
为了评估B7、CTLA 4和CD 28在慢性滑膜炎发病机制中的作用，我们分析了这些细胞表面分子在类风湿性关节炎、骨关节炎和银屑病关节炎患者以及正常对照中的表达和功能。类风湿性滑膜的免疫过氧化物酶染色显示30%的T细胞与抗B7单克隆抗体的反应性，相反，骨关节炎和正常滑膜，其中没有看到这样的染色。此外，通过流式细胞术分析，类风湿性滑液T细胞中B7阳性（平均20%，范围0 - 96%），通过抗B7 mAb或CTLA 4 IG融合蛋白染色测定，而外周血T细胞中未检测到B7表达（平均1%）。为了分析B7在滑液T细胞上表达的功能重要性，我们使用这些细胞作为原代同种异体MLC中的刺激细胞。纯化的滑液T细胞是比成对的外周血T细胞强得多的刺激细胞，并且导致同种异体T细胞增殖增加五倍。此外，添加CTLA 4 IG融合蛋白可显着抑制纯化的滑膜T细胞诱导的增殖（77%）。此外，抗B7 mAb（37%）、抗CTLA 4 mAb（33%）和抗CD 28 mAb的Fab片段（52%）部分抑制原发性MLC。功能性B7的表达，以及MHC II类分子表达的增加，表明滑膜T细胞可以作为功能性APC，并能够通过CD 28活化途径进行自分泌刺激。
To assess the role of B7, CTLA4, and CD28 in the pathogenesis of chronic synovitis we analyzed the expression and function of these cell surface molecules in patients with rheumatoid arthritis, osteoarthritis, and psoriatic arthritis, and in normal controls. Immunoperoxidase staining of rheumatoid synovial membranes showed reactivity of 30% of T cells with anti-B7 mAb, in contrast to osteoarthritic and normal synovial membranes, in which no such staining was seen. In addition, rheumatoid synovial fluid T cells were positive by flow cytometric analysis for B7 (mean 20%, range 0 to 96%), as measured by staining with anti-B7 mAb or the CTLA4 Ig fusion protein, whereas no B7 expression was detected on peripheral blood T cells (mean 1%). To analyze the functional importance of B7 expressed on synovial fluid T cells, we used these cells as stimulator cells in primary allogeneic MLC. Purified synovial fluid T cells were far stronger stimulator cells compared with paired peripheral blood T cells and resulted in a fivefold greater increase in allogeneic T cell proliferation. Furthermore, the proliferation induced by purified synovial T cells was markedly inhibited by addition of the CTLA4 Ig fusion protein (77%). Moreover, anti-B7 mAb (37%), anti-CTLA4 mAb (33%), and Fab fragments of anti-CD28 mAb (52%) partially inhibited the primary MLC. The expression of functional B7, together with the increased expression of MHC class II molecules, indicates that synovial T cells may serve as functional APCs and may be capable of autocrine stimulation via the CD28 activation pathway.