权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Expression of T cell cytokines in the inflamed synovium from patients with rheumatoid arthritis

类风湿性关节炎患者炎症滑膜中T细胞细胞因子的表达

基本信息

批准号：
10670411
负责人：
YAMAMURA Masahiro
金额：
$ 1.79万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

The inflamed synovium of rheumatoid arthritis (RA) is characterized by massive infiltration of CD4+ T cells. It has recently been indicated that the IFN-γ-dominant Th1-type immune response is involved in the disease process of RA. The cytokine profile of CD4+ T cells infiltrates was compared with that of peripheral blood CD4+ CD45+ T cells in patients with RA by intracellular cytokine staining and flow cytometric analysis. We found that synovial tissue CD4+ T cells contained more Th1-type (IFN-γ) and Th0 type (IFN-γ+IL-4) cells, and that there were unique CD4+ T cells such as those producing both IFN-γ and IL-10/IL-13.We also found that fibroblast cell lines from RA synovial tissues spontaneously produced the IL-2-like cytokines Il7 and IL-15, which was augmented by stimulation with IL-1 and TNF-α. IL-15 was able to stimulate the proliferation of synovial tissue T cells more potently than IL-2.Furthermore, the IFN-γ-inducing factor, IL-18, was strongly expressed in the inflammatory joint of RA. Although IL-18 had only minute effect, the level of IFN-γ produced by RA synovial tissues with IL-12 was significantly increased by IL-18, but over 50% reduced by the presence of anti-IL-18.Taken together, our data support that the immune inflammatory response in RA is mediated predominantly by Th1 cells. Il-15, produced by macrophages and synovial fibroblasts, appears to be the important stimulating factor for T cells. Local IFN-γ production may be regulated primarily by IL-12 and readily augmented by the abundance of IL-18 in RA joints.

类风湿关节炎(RA)滑膜炎症的特点是大量的CD4+T细胞渗入。最近的研究表明，干扰素-γ主导的Th1型免疫反应参与了类风湿关节炎的发病过程。采用细胞内细胞因子染色和流式细胞术分析比较类风湿关节炎患者外周血和外周血中CD4+T细胞的细胞因子水平。我们发现滑膜组织中的CD_4+T细胞含有较多的Th1型(干扰素-γ)和Th0型(干扰素-γ+IL-4)细胞，并且存在独特的CD_4+T细胞，如同时产生干扰素-γ和IL-10/IL-13的细胞。我们还发现，来自RA滑膜组织的成纤维细胞系自发地产生IL-2样细胞因子IL-7和IL-15，IL-1和IL-α刺激可使其增强。IL-15对滑膜组织T细胞增殖的刺激作用强于IL-2。此外，IL-18诱导因子IL-18在RA炎症关节中有较强的表达。尽管IL-18对RA滑膜组织产生的干扰素-γ的影响很小，但IL-18可显著增加RA滑膜组织产生的干扰素-Th1，而抗IL-18的作用可使其下降50%以上，提示RA的免疫炎症反应主要是由Th1细胞介导的。IL-15由巨噬细胞和滑膜成纤维细胞产生，是T细胞的重要刺激因子。局部干扰素-γ的产生可能主要受IL-12的调节，并很容易被RA关节中丰富的IL-18所增强。