T cell receptor of Fas-sensitive T cells in rheumatoid synovium.
T cell receptor of Fas-sensitive T cells in rheumatoid synovium.
复制标题
类风湿滑膜中 Fas 敏感 T 细胞的 T 细胞受体。
DOI：
10.4049/jimmunol.158.4.1965
复制
发表时间：
1997
影响因子：
4.4
通讯作者：
K. Nishioka
中科院分区：
文献类型：
--
作者：
T. Sumida;T. T. Hoa;H. Asahara;T. Hasunuma;K. Nishioka
类风湿关节炎（RA）患者滑膜细胞和CD 3 + T细胞存在凋亡。为了分析类风湿关节炎滑膜细胞凋亡的发病机制，我们检测了Fas抗原，Fas配体（Fas-L）和TCR的表达对抗Fas单克隆抗体敏感的T细胞。免疫组化和流式细胞术检测表明，滑膜中40 ~ 60%的CD 3 + T细胞表达Fas Ag。用逆转录-PCR方法观察到类风湿性关节炎滑膜浸润的T细胞上Fas-L过表达。这些结果表明RA滑膜细胞凋亡是由Fas/Fas-L途径介导的。PCR-单链构象多态性清楚地表明，超过50%的T细胞，积累在滑膜中被去除孵育与抗Fas单克隆抗体在体外24小时，表明这些细胞是Fas敏感的。连接序列分析显示，在积累的Fas敏感性T细胞克隆的CDR 3区域中存在几个保守的氨基酸基序（ERxxxSMNTE、IAAEGLLG、QxEGxD、VPD、TLAGxYNEQ、EPSE、LTNxGEL、QGK、NIP、GLL和KWT），而在Fas抗性克隆中未检测到这些基序。总之，我们的研究结果支持的概念，Fas敏感的T细胞在类风湿关节炎滑膜产生的Ag刺激和识别相对有限的T细胞表位上的自身抗原，这表明抗Fas单克隆抗体的敏感性可能是一个选择性标记激活的自身反应性T细胞在RA。
Apoptosis is found in synoviocytes and CD3+ T cells in the synovium of patients with rheumatoid arthritis (RA). To analyze the pathogenesis of apoptosis in rheumatoid synovium, we examined the expression of Fas Ag, Fas ligand (Fas-L), and TCR on T cells susceptible to anti-Fas mAbs. Fas Ag is expressed on 40 to 60% of CD3+ T cells in the synovium as measured by immunohistochemical and flow cytometry methods. It was observed by the reverse transcription-PCR method that Fas-L is overexpressed on T cells infiltrating the rheumatoid synovium. These results suggest that apoptosis in RA synovium is mediated by the Fas/Fas-L pathway. PCR-single-strand conformation polymorphism clearly demonstrated that more than 50% of T cells that accumulate in synovium are removed by incubation with anti-Fas mAbs for 24 h in vitro, indicating that these cells are Fas sensitive. Junctional sequence analysis revealed several conserved amino acids motifs (ERxxxSMNTE, IAAEGLLG, QxEGxD, VPD, TLAGxYNEQ, EPSE, LTNxGEL, QGK, NIP, GLL, and KWT) in the CDR3 region of accumulated Fas-sensitive T cell clones, whereas these motifs were not detected in Fas-resistant clones. In conclusion, our findings support the notion that Fas-sensitive T cells in rheumatoid synovium are generated by Ag stimulation and recognize relatively limited T cell epitopes on autoantigens, suggesting that susceptibility to anti-Fas mAbs might be a selection marker for activated autoreactive T cells in RA.