Role of cell adhesion molecules in the selective extravasculat T cell migration and in the pathogenesis of autoimmune diseases.

T细胞从循环向炎症位点的迁移可能在自身免疫性疾病（如类风湿关节炎和干燥综合征）的发病机制中发挥重要作用。我们将人脐带静脉内皮细胞（EC）作为单层细胞在组织培养板上的胶原凝胶上培养，建立了体外血管模型。因此，将来自外周血的T细胞在EC单层上共培养后，计数通过EC迁移的T细胞，以及粘附在EC上但未迁移的T细胞。这些T细胞也可以从胶原凝胶中回收，用于评估其表面表型。可以通过内皮细胞迁移的T细胞由一小部分CD4^+辅助性T细胞（占外周血T细胞的1-5%）组成，这些T细胞强烈表达活化相关抗原，如CD25、CD26、vla2和vla3。用抗hla -3抗体预处理T细胞或用抗层粘连蛋白抗体预处理EC可显著抑制T细胞通过EC单层膜的迁移。与骨关节炎患者的正常受试者相比，类风湿关节炎患者外周血淋巴细胞中迁移T细胞亚群的数量减少。临床上滑膜炎活动性越强的患者迁移T细胞减少越多。用金化合物（GST）处理可能通过抑制迁移T细胞亚群的激活和产生显著减少迁移T细胞的数量。

T cell migration from circulation to the locus of inflammation may play an important role in the pathogenesis of autoimmune diseases, such as rheumatoid arthritis and Sjogren's syndrome. We have developed an in vitro model of blood vessels by culturing endothelial cells (EC) obtained from human umbilical cord veins as monolayr on collagen gels in tissue culture plate. Thus, after co-culturing T cells from peripheral blood on EC monolayr, T cells migrated through EC, as well as T cells that adhered to EC but did not migrate, were counted. Those T cells could also be recovered from collagen gels for the assessment of their surface phenotypes.T cells that can migrate through endothelial cells, consist of a minor subset of CD4^+ helper T cells (1-5% of peripheral blood T cells) that strongly expressed activation-related antigens such as CD25, CD26, VLA-2 and VLA-3. Pretreatment of T cells with anti-VLA-3 antibody, or EC with anti-laminin antibody significantly inhibited the migration of T cells through EC monolayrs.The number of migrating T cell subset in peripheral blood lymphocytes was decreased in patients with rheumatoid arthritis, as compared to normal subjects of patients with osteoarthritis. Patients with clinically more active synovitis had more decreased migrating T cells. Treatment with gold compound (GST) significantly decreased the number of migrating T cells probably by inhibiting the activation and production of migrating T cell subset.