Jung S, Krämer S, Schluesener H J, Hünig T, Toyka K, Hartung H P
Department of Neurology, University of Würzburg, Germany.
J Immunol. 1992 Jun 15;148(12):3768-75.
The mAb R73 directed to the TCR-alpha/beta of rat lymphocytes was tested for its therapeutic potential during the effector phase of experimental autoimmune neuritis (EAN) in Lewis rats. EAN can be actively induced by immunization with bovine peripheral nerve myelin, bovine P2 protein, or a peptide containing its neuritogenic epitope and serves as a model of the human Guilain-Barré syndrome. Adoptive transfer of activated P2-specific T lymphocytes also produces the monophasic disease (AT-EAN) characterized by inflammation and demyelination of peripheral nerves and highlights the central role of T lymphocytes in the pathogenesis of EAN. A single administration of the mAb R73 immediately after injection of activated P2-specific T line cells completely prevented the development of clinical and electrophysiologic signs of EAN in most animals and greatly alleviated the disease in the others. In further experiments mAb R73 was applied after the appearance of first clinical signs of EAN actively induced by immunization with a neuritogenic peptide or bovine peripheral nerve myelin. In both cases the anti-TCR-alpha/beta mAb reversed clinical signs of EAN and prevented the development of peripheral nerve dysfunction. In vivo and in vitro data suggest that impairment of Ag recognition and T cell function by occupancy of the TCR and R73-induced TCR-modulation rather than depletion of TCR-alpha/beta-bearing lymphocytes is the decisive mechanism underlying suppression of EAN that is apparent already within 48 h of the first R73 injection.
针对大鼠淋巴细胞TCR-α/β的单克隆抗体R73，在Lewis大鼠实验性自身免疫性神经炎（EAN）效应阶段，对其治疗潜力进行了测试。EAN可通过用牛周围神经髓磷脂、牛P2蛋白或含其神经原性表位的肽进行免疫主动诱导，它是人类吉兰 - 巴雷综合征的模型。活化的P2特异性T淋巴细胞的过继转移也会产生以周围神经炎症和脱髓鞘为特征的单相疾病（AT-EAN），并突出了T淋巴细胞在EAN发病机制中的核心作用。在注射活化的P2特异性T系细胞后立即单次给予单克隆抗体R73，在大多数动物中完全阻止了EAN临床和电生理体征的发展，在其他动物中也大大减轻了疾病。在进一步的实验中，在用神经原性肽或牛周围神经髓磷脂免疫主动诱导出EAN的首个临床体征后，应用单克隆抗体R73。在这两种情况下，抗TCR-α/β单克隆抗体都逆转了EAN的临床体征，并阻止了周围神经功能障碍的发展。体内和体外数据表明，通过占据TCR和R73诱导的TCR调节来损害抗原识别和T细胞功能，而非耗竭携带TCR-α/β的淋巴细胞，是抑制EAN的决定性机制，在首次注射R73后48小时内就已明显可见。
