Myelin/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice
Myelin/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice
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DOI：
10.1172/jci200315861
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发表时间：
2003-08-01
影响因子：
15.9
通讯作者：
Pham-Dinh, D
中科院分区：
文献类型：
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作者：
Delarasse, C;Daubas, P;Pham-Dinh, D
我们研究了髓鞘/少突胶质细胞糖蛋白（MOG）非常有效的致脑炎性的免疫学基础，MOG是CNS中髓鞘的一种次要成分，广泛用于诱导实验性自身免疫性脑脊髓炎（EAE）。为了这个目的，我们产生了一个突变小鼠缺乏一个功能性的mog基因。这种MOG缺陷小鼠没有临床或组织学异常，使我们能够直接评估MOG作为EAE靶自身抗原的作用。与WT小鼠相比，其在用全髓磷脂免疫后发展严重的EAE，MOG缺陷型小鼠具有轻度表型，表明抗MOG应答是针对髓磷脂的自身免疫应答的主要致病组分。此外，虽然MOG转录物在淋巴器官中以微量表达，但MOG缺陷型小鼠和V/T小鼠均显示出针对MOG胞外结构域（包括免疫显性MOG 35-55 T细胞表位）的类似T和B细胞应答。此外，在MOG（+）/（+）和MOG（-）/（-）小鼠之间没有观察到T细胞对覆盖完整小鼠MOG序列的重叠肽的应答的精细特异性的差异。此外，在过继转移后，来自WT小鼠的MOG特异性T细胞和来自MOG缺陷型小鼠的那些细胞具有相同的致病性。WT C57 BL/6小鼠中对MOG的免疫耐受性的完全缺乏可能是抗MOG免疫应答的高致病性以及大多数动物品系对MOG诱导的EAE的高易感性的原因。
We studied the immunological basis for the very potent encephalitogenicity of myelin/oligodendrocyte glycoprotein (MOG), a minor component of myelin in the CNS that is widely used to induce experimental autoimmune encephalomyelitis (EAE). For this purpose, we generated a mutant mouse lacking a functional mog gene. This MOG-deficient mouse presents no clinical or histological abnormalities, permitting us to directly assess the role of MOG as a target autoantigen in EAE. In contrast to WT mice, which developed severe EAE following immunization with whole myelin, MOG-deficient mice had a mild phenotype, demonstrating that the anti-MOG response is a major pathogenic component of the autoimmune response directed against myelin. Moreover, while MOG transcripts are expressed in lymphoid organs in minute amounts, both MOG-deficient and V/T mice show similar T and B cell responses against the extracellular domain of MOG, including the immunodominant MOG 35-55 T cell epitope. Furthermore, no differences in the fine specificity of the T cell responses to overlapping peptides covering the complete mouse MOG sequence were observed between MOG(+)/(+) and MOG(-)/(-) mice. In addition, upon adoptive transfer, MOG-specific T cells from WT mice and those from MOG-deficient mice are equally pathogenic. This total lack of immune tolerance to MOG in WT C57BL/6 mice may be responsible for the high pathogenicity of the anti-MOG immune response as well as the high susceptibility of most animal strains to MOG-induced EAE.