Stamenkovic I, Stegagno M, Wright K A, Krane S M, Amento E P, Colvin R B, Duquesnoy R J, Kurnick J T
Department of Pathology, Harvard Medical School, Boston, MA.
Proc Natl Acad Sci U S A. 1988 Feb;85(4):1179-83. doi: 10.1073/pnas.85.4.1179.
Synovial membranes in patients with rheumatoid arthritis as well as other types of chronic destructive inflammatory arthritis contain infiltrates of activated T lymphocytes that probably contribute to the pathogenesis of the disease. In an effort to elucidate the nature of these infiltrates, interleukin 2 (IL-2)-responsive T lymphocytes were grown out of synovial fragments from 14 patients undergoing surgery for advanced destructive inflammatory joint disease. Eleven of the samples examined were from patients with classical rheumatoid arthritis, while three others were obtained from individuals with clinical osteoarthritis. Southern blot analysis of T-cell receptor (TCR) beta-chain genes in 13 of 14 cultures showed distinct rearrangements, indicating that each culture was characterized by the predominance of a limited number of clones. T-cell populations from peripheral blood stimulated with a variety of activators and expanded with IL-2 did not demonstrate evidence of similar clonality in long-term culture. These results suggest that a limited number of activated T-cell clones predominate at the site of tissue injury in rheumatoid synovial membranes as well as in other types of destructive inflammatory joint disease. Further characterization of these T-cell clones may aid our understanding of the pathogenesis of these rheumatic disorders.
类风湿关节炎患者以及其他类型慢性破坏性炎症性关节炎患者的滑膜中含有活化T淋巴细胞浸润,这些浸润可能促成了疾病的发病机制。为了阐明这些浸润的性质,从14例因晚期破坏性炎症性关节病接受手术的患者的滑膜碎片中培养出白细胞介素2(IL-2)反应性T淋巴细胞。所检测的样本中有11份来自典型类风湿关节炎患者,另外3份取自临床骨关节炎患者。在14个培养物中的13个中,对T细胞受体(TCR)β链基因进行的Southern印迹分析显示出明显的重排,表明每个培养物的特征是有限数量的克隆占优势。用多种激活剂刺激并经IL-2扩增的外周血T细胞群体在长期培养中未显示出类似克隆性的证据。这些结果表明,在类风湿滑膜以及其他类型的破坏性炎症性关节病的组织损伤部位,有限数量的活化T细胞克隆占主导地位。对这些T细胞克隆的进一步表征可能有助于我们理解这些风湿性疾病的发病机制。