Characterization of Relapsing-Remitting and Chronic Forms of Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice
Characterization of Relapsing-Remitting and Chronic Forms of Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice
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DOI：
10.1002/glia.20935
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发表时间：
2010-03-01
期刊：
影响因子：
6.2
通讯作者：
David, Samuel
中科院分区：
文献类型：
--
作者：
Berard, Jennifer L.;Wolak, Kevin;David, Samuel
多发性硬化症（MS）是一种中枢神经系统（CNS）的自身免疫性脱髓鞘疾病。与多发性硬化症一样，动物模型实验性自身免疫性脑脊髓炎（EAE）以中枢神经系统炎症和脱髓鞘为特征，并可遵循复发缓解（RR）或慢性（CH）病程。这些不同形式的EAE背后的分子和病理差异尚不完全清楚。我们比较了同一小鼠品系（C57BL/6）使用相同抗原产生的RR-和CH-EAE的差异。在两组小鼠临床评分相似的疾病高峰期，与RR-EAE相比，CH-EAE与病变负担、髓磷脂损失、轴突损伤和趋化因子/细胞因子表达增加有关。我们进一步发现，炎症和髓磷脂损失在CH-EAE的晚期继续恶化，而这些特征在RR-EAE的等效阶段基本得到解决。此外，在这些后期阶段，CH-EAE的轴突损失比RR-EAE更严重。我们还证明CH-EAE与CNS中CD8(+) T细胞的更大优势相关，这些细胞表现出MOG（35-55）抗原特异性。因此，这些研究表明，早在疾病的高峰阶段，RR-和CH-EAE在免疫细胞谱、趋化因子/细胞因子反应和组织病理学特征上就存在显著差异。这些数据还表明，该CH-EAE模型表现出慢性进行性疾病的病理特征，并表明持续的慢性表型是由于轴突损失、髓磷脂损失和持续炎症的结合。(C) 2009乳清乳白。公司。
Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system (CNS). Like MS, the animal model experimental autoimmune encephalomyelitis (EAE) is characterized by CNS inflammation and demyelination and can follow a relapsing-remitting (RR) or chronic (CH) disease course. The molecular and pathological differences that underlie these different forms of EAE are not fully understood. We have compared the differences in RR- and CH-EAE generated in the same mouse strain (C57BL/6) using the same antigen. At the peak of disease when mice in both groups have similar clinical scores, CH-EAE is associated with increased lesion burden, myelin loss, axonal damage, and chemokine/cytokine expression when compared with RR-EAE. We further showed that inflammation and myelin loss continue to worsen in later stages of CH-EAE, whereas these features are largely resolved at the equivalent stage in RR-EAE. Additionally, axonal loss at these later stages is more severe in CH-EAE than in RR-EAE. We also demonstrated that CH-EAE is associated with a greater predominance of CD8(+) T cells in the CNS that exhibit MOG(35-55) antigen specificity. These studies therefore showed that, as early as the peak stage of disease, RR- and CH-EAE differ remarkably in their immune cell profile, chemokine/cytokine responses, and histopathological features. These data also indicated that this model of CH-EAE exhibits pathological features of a chronic-progressive disease profile and suggested that the sustained chronic phenotype is due to a combination of axonal loss, myelin loss, and continuing inflammation. (C) 2009 whey-Liss. Inc.