Augmented production of chemokines by the interaction of type II collagen-reactive T cells with rheumatoid synovial fibroblasts
Augmented production of chemokines by the interaction of type II collagen-reactive T cells with rheumatoid synovial fibroblasts
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DOI：
10.1002/art.20133
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发表时间：
2004-04-01
影响因子：
--
通讯作者：
Kim, HY
中科院分区：
文献类型：
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作者：
Min, DJ;Cho, ML;Kim, HY
Objective.研究类风湿性关节炎（RA）患者关节中II型胶原（CII）反应性T细胞对趋化因子产生的影响。T细胞增殖反应牛CH测定滑液（SF）单核细胞和外周血单核细胞。将CII刺激的T细胞与成纤维细胞样滑膜细胞（FLS）共培养。采用酶联免疫吸附法检测血清、SF、CII刺激的T细胞和FLS共培养上清液中白细胞介素-8（IL-8）、单核细胞趋化蛋白1（MCP-1）和巨噬细胞炎性蛋白1 α（MIP-1 α）的表达。SF中IL-8、MCP-1和MIP-1 α水平显著高于RA患者配对血清。SF中IL-8、MCP-1和MIP-1 α的水平显著升高。与T细胞对CII的反应相关。当FLS与CII刺激的T细胞共培养时，IL-8、MCP-1和MIP-1a的产生显著增加。这种增加与对CII的T细胞增殖反应密切相关。CII刺激的T细胞与FLS共培养产生的趋化因子主要通过CD 40配体-CD 40结合的直接细胞间接触介导。我们的数据表明，类风湿关节炎关节中存在的CII反应性T细胞可以通过与FLS相互作用增加趋化因子如IL-8、MCP-1和MIP-1 α的产生。这种趋化因子的产生是由细胞-细胞接触介导的，包括CD 40配体-CD 40接合。这些结果表明，CII反应性T细胞在类风湿性滑膜炎症过程的放大和持续中起着至关重要的作用。
Objective. To determine the impact of type II collagen (CII)-reactive T cells on the production of chemokines in the joints of patients with rheumatoid arthritis (RA).Methods. T cell proliferative responses to bovine CH were assayed in synovial fluid (SF) mononuclear cells and peripheral blood mononuclear cells. CII-stimulated T cells were cocultured with fibroblast-like synoviocytes (FLS). The expression of interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1alpha (MIP-1alpha) in the sera, SF, and supernatant of the CII-stimulated T cells and FLS coculture was measured by enzyme-linked immunosorbent assays.Results. The levels of IL-8, MCP-1, and MIP-1alpha in SF were significantly higher than those in paired sera of RA patients. IL-8, MCP-1, and MIP-1alpha levels in SF were strongly. correlated with T cell responses to CII. When FLS were cocultured with CII-stimulated T cells, the production of IL-8, MCP-1, and MIP-1a was significantly increased. This increase correlated well with the T cell proliferative response to CII. Chemokine production by coculture of CII-stimulated T cells and FLS was mediated mainly by direct cell-cell contact through CD40 ligand-CD40 engagement.Conclusion. Our data indicate that the presence of CII-reactive T cells in RA joints can increase the production of chemokines such as IL-8, MCP-1, and MIP-1alpha through interaction with FLS. This chemokine production is mediated by cell-cell contact, including CD40 ligand-CD40 engagement. These results suggest that CII-reactive T cells play a crucial role in the amplification and perpetuation of the inflammatory process in the rheumatoid synovium.