Min Do-June, Cho Mi-La, Lee Sang-Heon, Min So-Youn, Kim Wan-Uk, Min Jun-Ki, Park Sung-Hwan, Cho Chul-Soo, Kim Ho-Youn
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea.
Arthritis Rheum. 2004 Apr;50(4):1146-55. doi: 10.1002/art.20133.
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).
T cell proliferative responses to bovine CII 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 1 alpha (MIP-1 alpha) in the sera, SF, and supernatant of the CII-stimulated T cells and FLS coculture was measured by enzyme-linked immunosorbent assays.
The levels of IL-8, MCP-1, and MIP-1 alpha in SF were significantly higher than those in paired sera of RA patients. IL-8, MCP-1, and MIP-1 alpha 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-1 alpha 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.
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-1 alpha 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.
确定II型胶原（CII）反应性T细胞对类风湿关节炎（RA）患者关节中趋化因子产生的影响。
检测滑膜液（SF）单个核细胞和外周血单个核细胞对牛CII的T细胞增殖反应。将CII刺激的T细胞与成纤维细胞样滑膜细胞（FLS）共培养。通过酶联免疫吸附测定法测量CII刺激的T细胞和FLS共培养的血清、SF及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1α（MIP-1α）的表达。
RA患者SF中IL-8、MCP-1和MIP-1α水平显著高于配对血清中的水平。SF中IL-8、MCP-1和MIP-1α水平与T细胞对CII的反应密切相关。当FLS与CII刺激的T细胞共培养时，IL-8、MCP-1和MIP-1α的产生显著增加。这种增加与T细胞对CII的增殖反应密切相关。CII刺激的T细胞与FLS共培养产生趋化因子主要通过CD40配体-CD40结合的直接细胞间接触介导。
我们的数据表明，RA关节中CII反应性T细胞的存在可通过与FLS相互作用增加IL-8、MCP-1和MIP-1α等趋化因子的产生。这种趋化因子的产生由细胞间接触介导，包括CD40配体-CD40结合。这些结果表明，CII反应性T细胞在类风湿滑膜炎症过程的放大和持续中起关键作用。
