Maurice M M, Res P C, Leow A, van Hall T, Daha M R, Struyk L, van den Elsen P, Breedveld F C, Verweij C L
Dept. of Rheumatology, University Hospital Leiden, The Netherlands.
Scand J Rheumatol Suppl. 1995;101:169-77. doi: 10.3109/03009749509100922.
The histopathological features of rheumatoid joint-inflammation suggest that an antigen-driven activation of T cells plays a central role in the onset and/or perpetuation of the inflammatory process. However, the disease-associated antigens responsible for the activation of T cells in the joint are unknown. In this project we study the response of IL-2 expanded T-cell lines from the synovial fluid (SF) of rheumatoid arthritis (RA) patients against autologous SF in a proliferation assay. Sixteen out of 32 RA patients were found to have CD4+ T cells that proliferate in response to autologous SF. 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. T cell clones reactive to autologous SF were isolated from SF-derived T-cell lines of two RA patients. All clones were of the CD4+, CD8-, alpha/beta+ phenotype. SF-reactivity of T-cell clones from the DR4/DR12-positive RA patient was restricted via the Dw4 subtype of DR4. SF reactivity of T cells of the DR12/DR15 patient was DP-restricted. Some of the T-cell clones responded specifically to autologous and not to allogeneic SF, whereas others revealed responsiveness against a limited number of allogeneic SF samples. The (restricted) specificity of T cells towards autologous SF antigens is indicative for heterogeneity of the epitopes recognized and argues against ubiquitous nonpolymorphic joint constituents as the relevant antigens recognized by the SF-autoreactive T cells.
类风湿性关节炎的组织病理学特征表明，抗原驱动的T细胞活化在炎症过程的发生和/或持续中起核心作用。然而，关节中负责激活T细胞的疾病相关抗原尚不清楚。在本项目中，我们在增殖试验中研究了类风湿性关节炎（RA）患者滑液（SF）中IL-2扩增的T细胞系对自体SF的反应。32例RA患者中有16例被发现其CD4+T细胞对自体SF有增殖反应。在发炎关节中存在能够对SF抗原作出反应的T细胞，表明这些T细胞在RA的发病机制中起积极作用。从两名RA患者的SF来源T细胞系中分离出对自体SF有反应的T细胞克隆。所有克隆均为CD4+、CD8-、α/β+表型。来自DR4/DR12阳性RA患者的T细胞克隆对SF的反应性通过DR4的Dw4亚型受到限制。DR12/DR15患者的T细胞对SF的反应性受DP限制。一些T细胞克隆对自体SF有特异性反应，而对同种异体SF无反应，而其他一些则显示对有限数量的同种异体SF样本有反应。T细胞对自体SF抗原的（受限）特异性表明所识别表位的异质性，并反对将普遍存在的非多态性关节成分作为SF自身反应性T细胞识别的相关抗原。
