Rat and human myelin oligodendrocyte glycoproteins induce experimental autoimmune encephalomyelitis by different mechanisms in C57BL/6 mice
Rat and human myelin oligodendrocyte glycoproteins induce experimental autoimmune encephalomyelitis by different mechanisms in C57BL/6 mice
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DOI：
10.4049/jimmunol.171.1.462
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发表时间：
2003-07-01
影响因子：
4.4
通讯作者：
Ruddle, NH
中科院分区：
文献类型：
--
作者：
Oliver, AR;Lyon, GM;Ruddle, NH
用大鼠髓鞘少突胶质细胞糖蛋白（MOG）细胞外igg样结构域免疫的C57BL/6小鼠发生实验性自身免疫性脑脊髓炎（EAE），其B细胞独立性和主要的单核CNS浸润类似于MOG 35-55诱导的小鼠。相比之下，人MOG蛋白诱导的EAE依赖于B细胞的多形核白细胞。人类MOG与大鼠MOG在几个残基上有所不同，包括在42号位置的一个用于丝氨酸取代的脯氨酸。人MOG 35-55的致脑性较弱，而大鼠MOG 42位的脯氨酸置换严重削弱了其致脑性。然而，人MOG 35-55具有免疫原性，可诱导增殖。ifn - γ和IL-3对人类，而对啮齿类动物MOG 35-55没有影响。人MOG蛋白诱导的EAE对B细胞的依赖性并不是因为B细胞需要Ag呈递，因为来自B细胞缺陷小鼠的脾脏细胞加工并呈递人和大鼠MOG蛋白给T细胞。人和大鼠MOG蛋白致病机制的不同，可能是由这些蛋白诱导的抗体不同造成的。然而，大鼠和人的MOG蛋白诱导的抗体在滴度和IgG亚类上是相同的。这些数据表明，EAE可以通过两种机制在C57BL/6小鼠中诱导，这取决于免疫原的性质：脑源性T细胞对大鼠MOG或啮齿动物MOG 35-55的反应，或脑源性B细胞对人类MOG蛋白表位的反应，最有可能与小鼠决定因子交叉反应。
C57BL/6 mice immunized with the extracellular Ig-like domain of rat myelin oligodendrocyte glycoprotein (MOG) developed experimental autoimmune encephalomyelitis (EAE) resembling that induced by rodent MOG 35-55 in its B cell independence and predominantly mononuclear CNS infiltrate. In contrast, human MOG protein-induced EAE was B cell dependent with polymorphonuclear leukocytes. Human MOG differs from rat MOG at several residues, including a proline for serine substitution at position 42. Human MOG 35-55 was only weakly encephalitogenic, and a proline substitution in rat MOG at position 42 severely attenuated its encephalitogenicity. However, human MOG 35-55 was immunogenic, inducing proliferation. and IFN-gamma and IL-3 to human, but not rodent MOG 35-55. The B cell dependence of EAE induced by human MOG protein was not due to a requirement for Ag presentation by B cells, because spleen cells from B cell-deficient mice processed and presented human and rat MOG proteins to T cells. The different pathogenic mechanisms of human and rat MOG proteins might result from different Abs induced by these proteins. However, rat and human MOG proteins induced Abs to mouse MOG that were equivalent in titer and IgG subclass. These data demonstrate that EAE can be induced in C57BL/6 mice by two mechanisms, depending on the nature of the immunogen: an encephalitogenic T cell response to rat MOG or rodent MOG 35-55, or an encephalitogenic B cell response to epitopes on human MOG protein that most likely cross-react with mouse determinants.