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: 6591312
• 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: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6591312
• 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

实验性过敏性脑脊髓炎（EAE），用作动物 多发性硬化症（MS）模型，可以通过过继的 转移中枢神经系统特异性的CD 4 + T细胞 (CNS)抗原虽然导致病理性的机制 EAE和MS的变化没有完全定义， 淋巴细胞通过CNS和CNS内的抗原呈递 是炎症发展的必要事件。 使用抗已知分子的单克隆抗体（mAb）进行的研究 在T细胞、内皮细胞或CNS神经胶质细胞上表达， 显示其可以抑制CNS炎症的诱导 在EAE模型中在本研究中，我们报道了单克隆抗体EAE-4A 2， 通过用大鼠小胶质细胞免疫小鼠获得，该细胞识别 先前未表征的分子， 活化的淋巴细胞，以及活化的CNS内皮细胞， 小胶质细胞：当筛选该抗体时， 来自CNS、淋巴结、胸腺和脾脏的组织，以及通过免疫- 沉淀研究后进行一维和二维蛋白质印迹， 表明它识别一种新型抗原用这种抗原治疗大鼠 纯化的4A 2 mAb导致EAE的完全抑制或 其诱导显著延迟和较轻的临床疾病 IFN-γ-4A2处理也导致T细胞数量减少， 单核细胞/巨噬细胞聚集在血管周围袖带内， 渗透到CNS实质中的α-4A 2抗体显然 不直接干扰T细胞功能或活力， 通过恢复和刺激CD 4+的能力证明 致脑炎肽特异性T细胞 4A 2处理的动物，以及来自含有抗体的T细胞增殖 这些数据表明，α-4A 2 mAb识别一种新的 在淋巴细胞、内皮细胞和巨噬细胞上表达的分子 这可能在造血细胞运输和启动 中枢神经系统炎症