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

细胞粘附分子在选择性血管外 T 细胞迁移和自身免疫性疾病发病机制中的作用。

• 批准号: 02670287
• 负责人: KANO Shogo
• 金额: $ 1.6万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670287/
• 关键词: T cell migration; Endothelial cells; Cell adhesion molecule; Rheumatoid arthritis; 血管外遊走性T細胞; 細胞接着分子; 慢性関節リウマチ; 血管内皮細胞; T細胞; 接着分子; 自己免疫疾患; リンパ球遊走; VLA

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.

T细胞从循环向炎症部位的迁移可能在自身免疫性疾病（如类风湿性关节炎和干燥综合征）的发病机制中起重要作用。我们建立了一种体外血管模型，将人脐静脉内皮细胞（EC）在胶原凝胶上单层培养。因此，在EC单层上共培养来自外周血的T细胞后，对迁移通过EC的T细胞以及粘附于EC但不迁移的T细胞进行计数。这些T细胞也可以从胶原凝胶中回收，用于评估它们的表面表型。可以通过内皮细胞迁移的T细胞由一小部分CD 4 ^+辅助性T细胞（占外周血T细胞的1-5%）组成，这些辅助性T细胞强烈表达活化相关抗原，如CD 25、CD 26、VLA-2和VLA-3。用抗VLA-3抗体预处理T细胞或用抗层粘连蛋白抗体预处理EC可明显抑制T细胞通过EC单层的迁移。与骨关节炎患者的正常受试者相比，类风湿性关节炎患者外周血淋巴细胞中迁移的T细胞亚群数量减少。临床上更活跃的滑膜炎患者有更多的减少迁移T细胞。金化合物（GST）处理可显著减少迁移性T细胞的数量，其机制可能与抑制迁移性T细胞亚群的活化和产生有关。