Chin Y H, Ye M W, Cai J P, Xu X M
Department of Microbiology, University of Miami School of Medicine, FL 33101, USA.
Immunology. 1996 Apr;87(4):559-65. doi: 10.1046/j.1365-2567.1996.490562.x.
Lymphocytes migrate from blood into lymph nodes (LN) of rats specifically at segments of venules lined by high endothelium (HEV). We have previously shown that pretreatment of LN HEV cells with pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), augments their adhesiveness for thoracic duct lymphocytes (TDL). Here we report that a mouse monoclonal antibody, 3C10, recognized tissue-specific endothelial determinants on rat LN HEV cells and blocked their adhesiveness for TDL and EL-4J cells transfected with rat L-selectin. In contrast, 3C10 antibody did not inhibit lymphocyte attachment to Peyer's patch (PP) frozen sections or cultured PP HEV cells. The antibody immunoprecipitated from LN HEV cells two proteins with apparent molecular weights of 90,000 and 50,000. The expression of 3C10 antigen on LN HEV cells was increased by incubation with TNF-alpha or IFN-gamma. Furthermore, pretreatment of cytokine-stimulated LN HEV cells with 3C10 antibody blocked TDL binding in a dose-dependent manner. In contrast, 3C10 antigen expression on LN HEV cells was significantly decreased following incubation of cells with transforming growth factor-beta 1 (TGF-beta 1). In addition, TGF-beta 1 also abrogated the adhesiveness of LN HEV cells stimulated with TNF-alpha, IFN-gamma or both cytokines. Together, these data suggest that endothelial determinants recognized by the 3C10 antibody are tissue-specific ligands for lymphocyte adhesion and cytokines such as TNF-alpha and TGF-beta differentially regulate their expression and function.
淋巴细胞从血液中迁移至大鼠的淋巴结（LN），具体是在内皮细胞较高的小静脉段（HEV）。我们之前已经表明，用促炎细胞因子如肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）预处理LN HEV细胞，可增强其对胸导管淋巴细胞（TDL）的黏附性。在此我们报告，一种小鼠单克隆抗体3C10可识别大鼠LN HEV细胞上的组织特异性内皮决定簇，并阻断其对TDL和转染了大鼠L-选择素的EL-4J细胞的黏附性。相比之下，3C10抗体并不抑制淋巴细胞与派伊尔结（PP）冰冻切片或培养的PP HEV细胞的附着。该抗体从LN HEV细胞中免疫沉淀出两种表观分子量分别为90,000和50,000的蛋白质。用TNF-α或IFN-γ孵育可增加LN HEV细胞上3C10抗原的表达。此外，用3C10抗体预处理细胞因子刺激的LN HEV细胞，可呈剂量依赖性地阻断TDL结合。相比之下，用转化生长因子-β1（TGF-β1）孵育细胞后，LN HEV细胞上3C10抗原的表达显著降低。此外，TGF-β1还消除了TNF-α、IFN-γ或两种细胞因子刺激的LN HEV细胞的黏附性。总之，这些数据表明，3C10抗体识别的内皮决定簇是淋巴细胞黏附的组织特异性配体，TNF-α和TGF-β等细胞因子可差异调节它们的表达和功能。
