Weissert R, Wallström E, Storch M K, Stefferl A, Lorentzen J, Lassmann H, Linington C, Olsson T
Neuroimmunology Unit, Center of Molecular Medicine L8:04, Karolinska Hospital, S-17176 Stockholm, Sweden.
J Clin Invest. 1998 Sep 15;102(6):1265-73. doi: 10.1172/JCI3022.
Experimental autoimmune encephalomyelitis (EAE) induced in the rat by active immunization with myelin-oligodendrocyte-glycoprotein (MOG) is mediated by synergy between MOG-specific T cells and demyelinating MOG-specific antibody responses. The resulting disease is chronic and displays demyelinating central nervous system (CNS) pathology that closely resembles multiple sclerosis. We analyzed major histocompatibility complex (MHC) haplotype influences on this disease. The MHC haplotype does not exert an all-or-none effect on disease susceptibility. Rather, it determines the degree of disease susceptibility, recruitment of MOG-specific immunocompetent cells, clinical course, and CNS pathology in a hierarchical and allele-specific manner. Major haplotype-specific effects on MOG-EAE map to the MHC class II gene region, but this effect is modified by other MHC genes. In addition, non-MHC genes directly influence both disease and T cell functions, such as the secretion of IFN-gamma. Thus, in MOG-EAE, allelic MHC class II effects are graded, strongly modified by other MHC genes, and overcome by effects of non-MHC genes and environment.
通过用髓鞘少突胶质细胞糖蛋白（MOG）主动免疫诱导大鼠产生的实验性自身免疫性脑脊髓炎（EAE），是由MOG特异性T细胞与脱髓鞘MOG特异性抗体反应之间的协同作用介导的。由此产生的疾病是慢性的，表现出与多发性硬化症极为相似的脱髓鞘中枢神经系统（CNS）病理学特征。我们分析了主要组织相容性复合体（MHC）单倍型对这种疾病的影响。MHC单倍型对疾病易感性并非产生全或无的效应。相反，它以分层和等位基因特异性的方式决定疾病易感性的程度、MOG特异性免疫活性细胞的募集、临床病程以及CNS病理学特征。对MOG-EAE的主要单倍型特异性效应定位于MHC II类基因区域，但这种效应会被其他MHC基因修饰。此外，非MHC基因直接影响疾病和T细胞功能，如γ干扰素的分泌。因此，在MOG-EAE中，MHC II类等位基因效应是分级的，会被其他MHC基因强烈修饰，并被非MHC基因和环境的效应所克服。
