Ransohoff R M, Tuohy V, Lehmann P
Samuel Rosenthal Multiple Sclerosis Research Laboratory, Reseach Institute, Cleveland Clinic Foundation, OH 44195.
Curr Opin Neurol. 1994 Jun;7(3):242-9. doi: 10.1097/00019052-199406000-00011.
New epidemiology and genetics data have supported the broad concept that multiple sclerosis represents an acquired autoimmunity, which is determined in part by inheritance. Furthermore, it is now widely believed that the pathogenesis of multiple sclerosis involves autoimmune reactivity that is directed against myelin proteins. Much of our understanding of myelin-directed autoimmunity has come from studies on experimental autoimmune encephalomyelitis, a T-cell-mediated, multiple sclerosis-like disease, which is provoked by immunizing animals with myelin proteins. During the past year, significant progress has been made in delineating immune reactivity to myelin antigens. Models that feature restricted epitope recognition and limited T-cell receptor gene utilization have been challenged (often by their original authors). Unifying new concepts include dynamic temporal diversification of the autoimmune response and clear-cut distinctions between the potential and engaged autoimmune repertoire. An abundance of new information about the biologic determinants of T-cell immunopathogenicity is leading rapidly to innovative therapeutic strategies.
新的流行病学和遗传学数据支持了这样一个广泛的概念，即多发性硬化症是一种后天获得性自身免疫性疾病，部分由遗传因素决定。此外，现在人们普遍认为，多发性硬化症的发病机制涉及针对髓鞘蛋白的自身免疫反应。我们对髓鞘定向自身免疫的许多理解来自于对实验性自身免疫性脑脊髓炎的研究，这是一种由T细胞介导的、类似于多发性硬化症的疾病，通过用髓鞘蛋白免疫动物诱发。在过去的一年里，在描绘对髓鞘抗原的免疫反应方面取得了重大进展。具有受限表位识别和有限T细胞受体基因利用特征的模型受到了挑战（通常是由其原作者提出）。统一的新概念包括自身免疫反应的动态时间多样化以及潜在和活跃的自身免疫库之间的明确区分。关于T细胞免疫致病性生物学决定因素的大量新信息正在迅速催生创新的治疗策略。
