Effector function of type II collagen-stimulated T cells from rheumatoid arthritis patients - Cross-talk between T cells and synovial fibroblasts
Effector function of type II collagen-stimulated T cells from rheumatoid arthritis patients - Cross-talk between T cells and synovial fibroblasts
复制标题
DOI：
10.1002/art.20106
复制
发表时间：
2004-03-01
影响因子：
--
通讯作者：
Kim, HY
中科院分区：
文献类型：
--
作者：
Cho, ML;Yoon, CH;Kim, HY
Objective.研究II型胶原（CII）刺激的T细胞对类风湿关节炎（RA）成纤维细胞样滑膜细胞（FLS）的效应功能，并确定其在RA发病中的作用。我们使用酶联免疫吸附试验来测量与抗原活化的T细胞共培养的FLS产生的白细胞介素-15（IL-15）、肿瘤坏死因子α（TNF α）和IL-18的水平。同样，我们分析了与FLS共孵育的RA T细胞产生干扰素-γ（IFN-γ）和IL-17的水平。为了研究CII刺激的T细胞和RA FLS之间的串扰，我们检测了在培养室中使用transwell膜分离T细胞和FLS的效果，以及添加抗体阻断CD 40连接的效果。RA患者血清中IL-15、TNF α、IFN γ和IL-17水平均显著高于正常对照组。在患者中，对CII具有较强T细胞增殖反应的组显示出较高水平的这些炎症介质。当与RA FLS共孵育时，这些T细胞诱导FLS产生IL-15、TNF α和IL-18，其强度与CII刺激的持续时间成比例增加。反过来，T细胞通过在共培养中分泌更高量的IL-17和IFN γ来响应FLS刺激。有趣的是，被CII激活较长时间的T细胞显示出对这些细胞因子的更强诱导。T细胞和FLS之间的相互作用似乎需要直接的细胞-细胞接触以及CD 40连接，至少部分是这样。通过CII的反复刺激，RA滑膜T细胞成为训练的效应细胞，诱导FLS产生促炎介质，而在此过程中，T细胞对FLS的激活信号变得更加敏感。
Objective. To investigate the effector function exerted by type II collagen (CII)-stimulated T cells on rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), and to determine their contribution to RA pathogenesis.Methods. We used enzyme-linked immunosorbent assays to measure the levels of interleukin-15 (IL-15), tumor necrosis factor alpha (TNFalpha), and IL-18 production by FLS that were cocultured with antigen-activated T cells. Likewise, we analyzed the levels of interferon-gamma (IFNgamma) and IL-17 production by RA T cells coincubated with FLS. To investigate the cross-talk between CII-stimulated T cells and RA FLS, we examined the effect of using a transwell membrane to separate T cells and FLS in a culture chamber, as well as the effect of adding an antibody to block CD40 ligation.Results. The levels of IL-15, TNFalpha, IFNgamma, and IL-17 were all significantly increased in the serum of RA patients compared with normal control serum. Among the patients, the group with a stronger T cell proliferation response to CII showed higher levels of these inflammatory mediators. When coincubated with RA FLS, these T cells induced the production of IL-15, TNFalpha, and IL-18 by FLS with an intensity that increased in proportion to the duration of CII stimulation. T cells, in turn, responded to FLS stimulation by secreting higher amounts of IL-17 and IFNgamma in coculture. Interestingly, T cells that were activated by CII for longer periods of time showed stronger induction of these cytokines. The cross-talk between T cells and FLS appeared to require direct cell-cell contact as well as CD40 ligation, at least in part.Conclusion. Through repeated stimulation by CII, RA synovial T cells became trained effector cells that induced the production of proinflammatory mediators by FLS, while in the process the T cells becoming more sensitized to the activation signal from FLS.