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幼年类风湿性关节炎滑膜T细胞中T细胞受体可变区基因使用的有限异质性。

Limited heterogeneity of T cell receptor variable region gene usage in juvenile rheumatoid arthritis synovial T cells.

作者信息

Sioud M, Kjeldsen-Kragh J, Suleyman S, Vinje O, Natvig J B, Førre O

机构信息

Institute of Immunology and Rheumatology, National Hospital, Oslo, Norway.

出版信息

Eur J Immunol. 1992 Sep;22(9):2413-8. doi: 10.1002/eji.1830220934.

Abstract

The aim of this study was to determine whether synovial fluid (SF) T cells in patients with juvenile rheumatoid arthritis (JRA) are restricted in their T cell receptor (TcR) gene repertoire. The quantitative polymerase chain reaction (QPCR) was used to compare the transcription of V beta and V alpha gene families in freshly isolated SF T cells, in interleukin-2 receptor-positive (IL-2R+) T cells and in peripheral blood (PB) T cells from 18 patients. Significantly less V beta families are detected in SF when compared with PB (p greater than 0.0003). The TcR V beta gene usage by IL-2R+ T cells was even less heterogeneous when compared with freshly isolated SF T cells (p greater than 0.0002). Freshly isolated SF T cells from the left and the right knees of four patients transcribed the same V beta families. Furthermore, we demonstrate that in SF the distribution of certain TcR V beta gene segments in CD4+ and CD8+ T cells differed from that in PB of the same patient. The TcR V alpha usage was studied in IL-2R+ T cells from six patients who had shown restriction in their SF TcR V beta gene usage. Only two to five TcR alpha transcripts were detected in three of these patients while a broad TcR V alpha usage was seen in the other three patients. Sequence analysis of the SF V beta 20 cDNA clones generated from the IL-2R+ T cells of two patients demonstrated an oligoclonal expansion. Taken together, our data could indicate an antigen- and/or superantigen-driven expansion of selected T cells in the synovial compartment.

摘要

本研究的目的是确定青少年类风湿性关节炎(JRA)患者的滑膜液(SF)T细胞在其T细胞受体(TcR)基因库中是否受到限制。采用定量聚合酶链反应(QPCR)比较了18例患者新鲜分离的SF T细胞、白细胞介素-2受体阳性(IL-2R+)T细胞和外周血(PB)T细胞中Vβ和Vα基因家族的转录情况。与PB相比,SF中检测到的Vβ家族明显较少(p>0.0003)。与新鲜分离的SF T细胞相比,IL-2R+ T细胞对TcR Vβ基因的使用甚至更不均匀(p>0.0002)。从4例患者的左膝和右膝新鲜分离的SF T细胞转录相同的Vβ家族。此外,我们证明,在SF中,同一患者的CD4+和CD8+ T细胞中某些TcR Vβ基因片段的分布与PB中的不同。对6例SF TcR Vβ基因使用受限的患者的IL-2R+ T细胞进行了TcR Vα使用情况的研究。其中3例患者仅检测到2至5种TcRα转录本,而其他3例患者则出现广泛的TcR Vα使用情况。对2例患者的IL-2R+ T细胞产生的SF Vβ20 cDNA克隆进行序列分析,显示为寡克隆扩增。综上所述,我们的数据可能表明滑膜腔中特定T细胞的抗原和/或超抗原驱动的扩增。

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