CELL CONTACT BETWEEN T-CELLS AND SYNOVIAL FIBROBLASTS CAUSES INDUCTION OF ADHESION MOLECULES AND CYTOKINES
CELL CONTACT BETWEEN T-CELLS AND SYNOVIAL FIBROBLASTS CAUSES INDUCTION OF ADHESION MOLECULES AND CYTOKINES
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DOI：
10.1002/jlb.54.5.399
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发表时间：
1993-11-01
影响因子：
5.5
通讯作者：
BLUE, ML
中科院分区：
文献类型：
--
作者：
BOMBARA, MP;WEBB, DL;BLUE, ML
体外培养的人活化T细胞与滑膜成纤维细胞样细胞黏附。本研究旨在研究T细胞-滑膜成纤维细胞相互作用对黏附分子和促炎细胞因子诱导的影响。采用敏感的Western印迹技术、聚合酶链式反应(PCR)扩增和荧光激活细胞分类(FACS)分析T细胞-滑膜成纤维细胞共培养中VCAM-1和ICAM-1的表达。培养2 h可诱导滑膜成纤维样细胞表达VCAM-1和ICAM-1，PCR扩增结果显示，滑膜成纤维细胞与T细胞相互作用后均可检测到VCAM-1的表达。VCAM-1和ICAM-1的上调仅限于滑膜成纤维细胞；T细胞不表达VCAM-1或增加ICAM-1。与T细胞-滑膜细胞相互作用相反，T细胞与真皮成纤维细胞的相互作用导致ICAM-1表达上调，但不上调VCAM-1，提示VCAM-1具有组织特异性调节。T细胞和滑膜成纤维细胞的相互作用也导致共培养上清液中肿瘤坏死因子(TNF)、干扰素-γ和白介素6水平的增加。在针对这些细胞因子的中和抗体中，只有抗肿瘤坏死因子抗体能显著抑制VCAM-1和ICAM-1的表达。当T细胞与滑膜细胞被一个允许介质交换但不允许细胞接触的小室分开时，VCAM-1和ICAM-1无法上调，细胞因子在共培养中的积累显著减少。我们的结果表明，T细胞和滑膜细胞在细胞接触时相互激活，T细胞和滑膜细胞特异性细胞因子的释放表明，类风湿滑膜中的滑膜成纤维细胞通过VCAM-1/ICAM-1慢性聚集和滞留单个核细胞的机制是细胞接触介导的和T细胞启动的。
Human activated T cells adhere to synovial fibroblast-like cells in vitro. The present study was conducted to investigate the consequences of T cell-synovial fibroblast interactions with regard to induction of adhesion molecules and proinflammatory cytokines. A sensitive Western blot technique, polymerase chain reaction (PCR) amplification, and fluorescence-activated cell sorter (FACS) analysis were used to analyze the induction of VCAM-1 and ICAM-1 expression in T cell-synovial fibroblast cocultures. VCAM-1 and ICAM-1 expression could be induced in synovial fibroblast-like cells by 2 h. PCR amplification showed that both forms of VCAM-1 mRNA are found after the interaction of synovial fibroblasts with T cells. Up-regulation of VCAM-1 and ICAM-1 was confined to synovial fibroblasts; T cells did not express VCAM-1 or increased ICAM-1. In contrast to the T cell-synoviocyte interaction, the interaction between T cells and dermal fibroblasts resulted in the up-regulation of ICAM-1 but not VCAM-1, suggesting tissue-specific regulation of VCAM-1. The T cell-synovial fibroblast interaction also resulted in increased levels of tumor necrosis factor (TNF), interferon-gamma, and interleukin-6 in coculture supernatant. Of the neutralizing antibodies used against these cytokines, only anti-TNF could significantly inhibit VCAM-1 and ICAM-1 expression. When T cells were separated from synoviocytes by a chamber that allowed medium exchange but no cell contact, VCAM-1 and ICAM-1 failed to be up-regulated and cytokine accumulation in cocultures was drastically reduced. Our results demonstrate mutual cell activation of T cells and synoviocytes upon cell contact as shown by the release of T cell- and synoviocyte-specific cytokines and suggest a cell contact-mediated and T cell-initiated mechanism for the chronic accumulation and retention of mononuclear cells via VCAM-1/ICAM-1 by synovial fibroblasts in the rheumatoid synovium.