Res P C, Struijk L, Leow A, Daha M R, van den Elsen P C, Breedveld F C
Department of Rheumatology, University Hospital, Leiden, The Netherlands.
Hum Immunol. 1994 Aug;40(4):291-8. doi: 10.1016/0198-8859(94)90028-0.
The immunopathology of inflamed joints in patients with RA is thought to result from an antigen-driven T-cell response. The antigen(s) responsible for the activation of synovial T cells, however, are as yet unidentified. In this study, we tested SF as a potential source of (auto)antigen(s). Five of 15 IL-2-expanded T-cell lines generated from SF cells of RA patients displayed a proliferative response to autologous SF. Five CD4+CD8-alpha beta TCR+SF-reactive T-cell clones obtained from responder T-cell lines were studied in more detail. Three T-cell clones from one RA patient were found to recognize epitopes in autologous SF in the context of DR4(Dw4), and two T-cell clones of another RA patient responded to autologous SF in the context of the HLA-DPB1*0401 gene product. The two DP-restricted clones and one of the DR-restricted clones did not proliferate to 50 SF samples of other RA patients, whereas the remaining DR-restricted clones responded to one allogeneic sample. Sequence analysis demonstrated that the latter clones expressed identical V beta 6.9 + TCR beta chains. This was also found for the (V beta 19+) DP-restricted clones. Proliferation of SF-reactive T cells was not only obtained with SF of the joint that had contained the T cells, but also with autologous SF of other affected joints. Together, these findings indicate that epitopes able to stimulate synovial T cells differ among RA patients, but may be similar within multiple joints of an individual patient. The presence of T cells able to respond to SF antigens in inflamed joints suggests that these T cells play an active role in the pathogenesis of RA.
类风湿关节炎（RA）患者炎症关节的免疫病理学被认为是由抗原驱动的T细胞反应所致。然而，负责激活滑膜T细胞的抗原尚未明确。在本研究中，我们测试了滑液（SF）作为（自身）抗原潜在来源的可能性。从RA患者的SF细胞中产生的15个白细胞介素-2扩增T细胞系中有5个对自体SF表现出增殖反应。对从反应性T细胞系中获得的5个CD4 + CD8-αβTCR + SF反应性T细胞克隆进行了更详细的研究。发现来自一名RA患者的3个T细胞克隆在DR4（Dw4）背景下识别自体SF中的表位，另一名RA患者的2个T细胞克隆在HLA-DPB1*0401基因产物背景下对自体SF有反应。两个受DP限制的克隆和一个受DR限制的克隆对其他RA患者的50份SF样本无增殖反应，而其余受DR限制的克隆对一份同种异体样本有反应。序列分析表明，后一组克隆表达相同的Vβ6.9 + TCRβ链。在（Vβ19 +）受DP限制的克隆中也发现了这一情况。SF反应性T细胞的增殖不仅在含有这些T细胞的关节的SF中出现，在其他受累关节的自体SF中也出现。总之，这些发现表明，能够刺激滑膜T细胞的表位在RA患者之间存在差异，但在个体患者的多个关节中可能相似。炎症关节中存在能够对SF抗原产生反应的T细胞表明，这些T细胞在RA的发病机制中发挥着积极作用。
