Genain C P, Nguyen M H, Letvin N L, Pearl R, Davis R L, Adelman M, Lees M B, Linington C, Hauser S L
Department of Neurology, University of California, San Francisco 94143, USA.
J Clin Invest. 1995 Dec;96(6):2966-74. doi: 10.1172/JCI118368.
In the human disease multiple sclerosis (MS), the immune mechanisms responsible for selective destruction of central nervous system myelin are unknown. In the common marmoset Callithrix jacchus, a unique demyelinating form of experimental allergic encephalomyelitis resembling MS can be induced by immunization with whole myelin. Here we show that the MS-like lesion can be reproduced by immunization against the extracellular domain of a single myelin protein, myelin/oligodendrocyte glycoprotein (MOG). By contrast, immunization against the quantitatively major myelin proteins myelin basic protein or proteolipid protein results in inflammation but little or no demyelination. Furthermore, in the presence of encephalitogenic (e.g., disease-inducing) T cells, the fully demyelinated lesion is reconstructed by systemic administration of IgG purified from whole myelin-, or MOG-immunized animals, and equally by a monoclonal antibody against MOG, but not by control IgG. Encephalitogenic T cells may contribute to the MS-like lesion through disruption of the blood-brain barrier that permits access of demyelinating antibody into the nervous system. The identification of MOG as a major target antigen for autoimmune demyelination in a nonhuman primate should facilitate development of specific immunotherapies for human MS.
在人类疾病多发性硬化症（MS）中，负责选择性破坏中枢神经系统髓鞘的免疫机制尚不清楚。在普通狨猴（Callithrix jacchus）中，通过用全髓鞘免疫可诱导出一种类似于MS的独特脱髓鞘形式的实验性变应性脑脊髓炎。在此我们表明，针对单一髓鞘蛋白髓鞘/少突胶质细胞糖蛋白（MOG）的细胞外结构域进行免疫可重现类似MS的病变。相比之下，针对数量上占主要的髓鞘蛋白髓鞘碱性蛋白或蛋白脂蛋白进行免疫会导致炎症，但几乎没有或没有脱髓鞘现象。此外，在存在致脑炎性（如致病的）T细胞的情况下，通过全身给予从全髓鞘免疫或MOG免疫动物中纯化的IgG，以及同样通过抗MOG单克隆抗体，可重建完全脱髓鞘的病变，但对照IgG则不能。致脑炎性T细胞可能通过破坏血脑屏障导致类似MS的病变，从而使脱髓鞘抗体进入神经系统。在非人类灵长类动物中确定MOG为自身免疫性脱髓鞘的主要靶抗原，应有助于开发针对人类MS的特异性免疫疗法。
