Duby A D, Sinclair A K, Osborne-Lawrence S L, Zeldes W, Kan L, Fox D A
Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
Proc Natl Acad Sci U S A. 1989 Aug;86(16):6206-10. doi: 10.1073/pnas.86.16.6206.
Although substantial evidence suggests that synovial T lymphocytes are critical in the pathogenesis of rheumatoid arthritis (RA), little is known regarding their antigenic specificities, antigen receptor gene rearrangements, and mechanisms of activation. To assess the extent of expansion of specific clones among RA synovial fluid T cells, Southern blot analyses of T-cell receptor (TCR) gene rearrangements were performed on 40 RA synovial fluid T-cell clones, as well as on both fresh and polyclonally activated T cells from RA synovial fluid, RA peripheral blood, and normal peripheral blood. Two of the clones had identical TCR rearrangement patterns, but the remainder were unique. The nonclonal RA T-cell samples showed the same pattern of TCR beta-chain rearrangement that was observed among normal peripheral blood T cells, indicating no dominant clonal T-cell population in these samples. It was noted that with sufficient exposure of autoradiograms of the Southern blots, discrete TCR gene rearrangements, representing in some cases common D beta J beta (D, diversity; J, joining) rearrangements, were evident in T cells from peripheral blood of normal individuals and patients with RA, as well as T cells from RA synovial fluid. Taken together, the findings indicate that only a minor degree of oligoclonality can be demonstrated among T lymphocytes from RA synovial fluid.
尽管大量证据表明滑膜T淋巴细胞在类风湿关节炎（RA）的发病机制中起关键作用，但对于它们的抗原特异性、抗原受体基因重排及激活机制却知之甚少。为评估RA滑膜液T细胞中特定克隆的扩增程度，我们对40个RA滑膜液T细胞克隆以及来自RA滑膜液、RA外周血和正常外周血的新鲜及多克隆激活T细胞进行了T细胞受体（TCR）基因重排的Southern印迹分析。其中两个克隆具有相同的TCR重排模式，但其余克隆均为独特模式。非克隆性RA T细胞样本显示出与正常外周血T细胞中观察到的相同的TCRβ链重排模式，表明这些样本中不存在占主导地位的克隆性T细胞群体。值得注意的是，Southern印迹放射自显影片充分曝光后，在正常个体和RA患者外周血T细胞以及RA滑膜液T细胞中，可明显看到离散的TCR基因重排，在某些情况下代表常见的DβJβ（D，多样性；J，连接）重排。综上所述，这些发现表明RA滑膜液中的T淋巴细胞仅表现出轻微程度寡克隆性。
