Steiner G, Tohidast-Akrad M, Witzmann G, Vesely M, Studnicka-Benke A, Gal A, Kunaver M, Zenz P, Smolen J S
Division of Rheumatology, University of Vienna, Ludwig Boltzmann-Institute of Rheumatology, Austria.
Rheumatology (Oxford). 1999 Mar;38(3):202-13. doi: 10.1093/rheumatology/38.3.202.
To investigate the production of cytokines by T cells in patients with rheumatoid arthritis (RA), reactive arthritis (REA) and osteoarthritis (OA).
The lymphokines interleukin (IL)-2, IL-4, interferon gamma (IFN-gamma) and tumour necrosis factor beta (TNF-beta), as well as the monokines IL-1, IL-6 and TNF-alpha, were measured by immunoassays in sera and synovial fluid (SF) from patients with RA, REA and OA. In addition, cytokine expression was studied by immunohistochemistry in synovial membrane tissue sections from patients with RA and OA.
Almost 60% of RA sera contained at least one of the cytokines investigated, though in low concentrations, whereas cytokines were generally not detectable in sera from REA and OA patients. In contrast, cytokines were found in virtually all SF; thus, the majority of SF from RA patients contained IFN-gamma (median level 17 pg/ml) in addition to the monokines IL-6 (4700 pg/ml) and TNF-alpha (157 pg/ml). IFN-gamma and IL-6 (but not TNF-alpha) were also frequently measured in SF from REA patients, whereas OA samples typically contained only IL-6. Immunohistochemical analysis of tissue sections from RA patients revealed lymphokine expression in 0.1-0.3% of T cells, particularly IL-2 and IFN-gamma, and to a lesser extent also IL-4. Interestingly, the expression of TNF-alpha and IL-6 by synovial T cells was also observed. The majority of cytokine-expressing T cells were CD4-positive T-helper cells typically found in perivascular areas, whereas cytokine-producing CD8-positive T cells were found distributed throughout the synovium. As expected, in specimens from OA patients, T cells were much less abundant and expression of cytokines could not be detected.
These data clearly demonstrate production of cytokines by T cells in RA synovial tissue, indicating that activated T cells play a role in the pathophysiological events of RA.
研究类风湿关节炎（RA）、反应性关节炎（REA）和骨关节炎（OA）患者T细胞产生细胞因子的情况。
采用免疫分析法检测RA、REA和OA患者血清及滑膜液（SF）中的淋巴细胞因子白细胞介素（IL）-2、IL-4、γ干扰素（IFN-γ）和肿瘤坏死因子β（TNF-β），以及单核因子IL-1、IL-6和TNF-α。此外，通过免疫组织化学研究RA和OA患者滑膜组织切片中的细胞因子表达。
近60%的RA血清中至少含有一种所研究的细胞因子，不过浓度较低，而REA和OA患者血清中通常检测不到细胞因子。相比之下，几乎所有的SF中都发现了细胞因子；因此，RA患者的大多数SF除了含有单核因子IL-6（4700 pg/ml）和TNF-α（157 pg/ml）外，还含有IFN-γ（中位水平17 pg/ml）。REA患者的SF中也经常检测到IFN-γ和IL-6（但不是TNF-α），而OA样本通常只含有IL-6。对RA患者组织切片的免疫组织化学分析显示，0.1-0.3%的T细胞中有淋巴细胞因子表达，特别是IL-2和IFN-γ，IL-4的表达程度较低。有趣的是，还观察到滑膜T细胞表达TNF-α和IL-6。大多数表达细胞因子的T细胞是通常在血管周围区域发现的CD4阳性辅助性T细胞，而产生细胞因子的CD8阳性T细胞则分布在整个滑膜中。正如预期的那样，在OA患者的标本中，T细胞数量少得多，且检测不到细胞因子表达。
这些数据清楚地证明了RA滑膜组织中T细胞产生细胞因子，表明活化的T细胞在RA的病理生理过程中起作用。
