Matsuda M, Ulfgren A K, Lenkei R, Petersson M, Ochoa A C, Lindblad S, Andersson P, Klareskog L, Kiessling R
Microbiology and Tumor Biology Center at Karolinska Institute, Stockholm, Sweden.
Scand J Immunol. 1998 Mar;47(3):254-62. doi: 10.1046/j.1365-3083.1998.00296.x.
Although T cells from patients with rheumatoid arthritis (RA) have previously been determined to have poor proliferative responses to a variety of stimuli, the underlying mechanism is not known. We have investigated the expression of the signal-transducing zeta molecule in subsets of T cells and natural killer (NK) cells derived from the peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) of RA patients using quantitative flow cytometry, Western blot analysis and immunohistochemistry. A decrease of zeta expression was apparent in all investigated lymphocyte subsets from the PBMC and SFMC of RA patients, as compared to the corresponding subsets from healthy age- and sex-matched controls. A less pronounced reduction of cell surface-located CD3 epsilon, CD4 and CD8 was also located in T cells from SFMC as compared to PBMC from RA patients. Biochemical demonstration of the low or absent CD3 zeta in PBMC from patients with RA was achieved by Western blot analysis. Immunohistochemical staining and image analysis also confirmed the low expression of zeta chains in synovial tissue of RA patients. The possibility that the decreased expression of zeta and of immune functions of T cells from RA patients may be related to the presence of free oxygen radicals, as we have previously reported in cancer patients, should be considered.
尽管先前已确定类风湿关节炎（RA）患者的T细胞对多种刺激的增殖反应较差，但其潜在机制尚不清楚。我们使用定量流式细胞术、蛋白质印迹分析和免疫组织化学，研究了来自RA患者外周血单个核细胞（PBMC）和滑膜液单个核细胞（SFMC）的T细胞亚群及自然杀伤（NK）细胞中信号转导ζ分子的表达。与年龄和性别匹配的健康对照的相应亚群相比，RA患者PBMC和SFMC中所有研究的淋巴细胞亚群的ζ表达均明显降低。与RA患者的PBMC相比，SFMC的T细胞中细胞表面定位的CD3ε、CD4和CD8的减少也不太明显。通过蛋白质印迹分析证实了RA患者PBMC中CD3ζ低表达或无表达。免疫组织化学染色和图像分析也证实了RA患者滑膜组织中ζ链的低表达。应考虑RA患者T细胞ζ表达降低和免疫功能下降可能与游离氧自由基的存在有关，正如我们先前在癌症患者中所报道的那样。
