INHIBITION OF EAE W/ MONOCLONAL ANTIBODY THAT RECOGNIZES NOVEL ANTIGEN

使用识别新抗原的单克隆抗体抑制 EAE

• 批准号: 6453758
• 负责人: KENNETH C WILLIAMS
• 金额: $ 11.11万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6453758
• 关键词: Mammalia; animal tissue; immunology; inflammation; nervous system

Experimental allergic encephalomyelitis (EAE), used as an animal model of multiple sclerosis (MS), can be induced by the adoptive transfer of CD4+ T cells that are specific for central nervous system (CNS) antigens While the mechanism(s) responsible for the pathological changes in EAE and MS are not fully defined, the traffic of lymphocytes through the CNS and antigen presentation within the CNS are required events for the development of inflammation Several studies using monoclonal antibodies (mAb) against known molecules expressed on T cells, endothelial cells, or CNS glial cells, have shown that it is possible to inhibit the induction of CNS inflammation in the EAE model In the present study we report a mAb TLD-4A2, obtained by immunizing mice with rat microglia, that recognizes a previously uncharacterized molecule The TLD-4A2 mAb stains resting and activated lymphocytes, as well as activated CNS endothelial cells and microglia The staining pattern of this antibody when screened on tissues from the CNS, lymph node, thymus, and spleen, and by immune- precipitation studies followed by one and two dimension western blots, suggest that it recognizes a novel antigen Treatment of rats with the purified 4A2 mAb resulted in either total inhibition of EAE or a significant delay in its induction and a milder clinical disease TLD-4A2 treatment also resulted in a decreased number T cells and monocyte/macrophages accumulating within perivascular cuffs and penetrating into the CNS parenchyma TLD-4A2 antibody apparently does not directly interfere with T cell function or viability as demonstrated by the ability to recover and stimulate CD4+ encephalitogenic peptide specific T cells from cervical lymph nodes of 4A2 treated animals, and from antibody containing T cell proliferation assays These data suggest that the TLD-4A2 mAb recognizes a novel molecule expressed on lymphocytes, endothelial cells, and macrophages that may play a role in hemato genous cell traffic and the initiation of CNS inflammation

实验性变态反应性脑脊髓炎(EAE)，用作动物 多发性硬化症(MS)模型，可通过过继诱导 中枢神经系统特异性CD4+T细胞的转移 (中枢神经系统)抗原而机制(S)负责病理 EAE和MS的变化没有完全定义， 中枢神经系统中的淋巴细胞和中枢神经系统内的抗原递呈 是炎症发展所必需的几个事件 利用抗已知分子的单抗进行研究 表达在T细胞、内皮细胞或中枢神经系统胶质细胞上 表明有可能抑制中枢神经系统炎症的诱导 在本研究的EAE模型中，我们报告了一种单抗TLD-4A2， 通过用大鼠小胶质细胞免疫小鼠而获得，它识别一个 以前未知的分子TLD-4A2单抗染色静息和 活化的淋巴细胞，以及活化的中枢神经系统内皮细胞和 小胶质细胞--该抗体筛选后的染色模式 来自中枢神经系统、淋巴结、胸腺和脾的组织，并通过免疫- 降水研究之后是一维和二维的蛋白质印迹， 提示它认识到了一种治疗大鼠的新抗原疗法 纯化的4A2单抗可完全抑制EAE或 显著延迟其诱发和较轻的临床疾病 TLD-4A2治疗还导致T细胞数量减少和 单核/巨噬细胞聚集在血管周围袖带和 TLD-4A2抗体明显穿透中枢神经系统实质 不会直接干扰T细胞的功能或活性 表现为恢复和刺激CD4+的能力 小鼠颈淋巴结生脑肽T细胞 4A2处理的动物，并从含有T细胞增殖的抗体 分析这些数据表明，TLD-4A2单抗识别一种新的 淋巴细胞、内皮细胞和巨噬细胞上表达的分子 可能在血源细胞的运输和启动中起作用 中枢神经系统炎症