MOUSE HEPATITIS-VIRUS A59-INDUCED DEMYELINATION CAN OCCUR IN THE ABSENCE OF CD8(+) T-CELLS
MOUSE HEPATITIS-VIRUS A59-INDUCED DEMYELINATION CAN OCCUR IN THE ABSENCE OF CD8(+) T-CELLS
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DOI：
10.1016/s0882-4010(95)90058-6
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发表时间：
1995-03-01
影响因子：
3.8
通讯作者：
WEISS, SR
中科院分区：
文献类型：
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作者：
GOMBOLD, JL;SUTHERLAND, RM;WEISS, SR
小鼠肝炎病毒引起C57 BL/6小鼠慢性脱髓鞘疾病虽然早期研究表明脱髓鞘是由于病毒对少突胶质细胞的直接细胞溶解作用，但越来越多的证据表明免疫系统参与脱髓鞘机制。在这项研究中，我们问是否脱髓鞘可以发生在功能性MHC I类表达和CD 8（+）T细胞的情况下。我们用MHV-A59感染缺乏β 2微球蛋白表达的转基因小鼠（β 2 M（-/-）小鼠）。在β（2）M（-/-）小鼠中，病毒比用于产生小鼠的任何一种亲本菌株都要致命得多;此外，虽然在β（2）M（-/-）小鼠中确实发生了CNS清除，但比C57 BL/6小鼠慢。这与CD 8（+）细胞在病毒清除中的重要性一致。由于beta（2）M（-/-）小鼠对感染的敏感性增加，只有低水平的病毒才能用于评估慢性疾病。即使在这些低水平下，脱髓鞘也确实发生在一些动物中。为了比较β（2）M（-/-）和C57 BL/6小鼠中的感染，我们使用了更高剂量的MHV-A59的减毒变体C12。与野生型A59相比，减毒变体在C57 BL/6小鼠中诱导较少的脱髓鞘，但观察到的水平与在β 2 M（-/-）小鼠中观察到的水平没有显著差异。因此，MHV诱导的脱髓鞘可以在缺乏MHC I类和CD 8（+）细胞的一些动物中发生。
Mouse hepatitis virus causes a chronic demyelinating disease in C57BL/6 mice. While early studies suggested demyelination is due to direct cytolytic effects of virus on oligodendrocytes, there is increasing evidence for the involvement of the immune system in the mechanism of demyelination. In this study we have asked whether demyelination can occur in the absence of functional MHC class I expression and CD8(+) T cells. We infected transgenic mice lacking expression of beta(2) microglobulin (beta(2)M(-/-) mice) with MHV-A59. In beta(2)M(-/-) mice, virus was much more lethal than in either of the parental strains used to produce the mice; furthermore, while clearance from the CNS did occur in beta(2)M(-/-) mice, it was slower than in C57BL/6 mice. This is consistent with the importance of CD8(+) cells in viral clearance. Because of the increased sensitivity of the beta(2)M(-/-) mice to infection, only low levels of virus could be used to evaluate chronic disease. Even at these low levels, demyelination did occur in some animals. To compare infection in beta(2)M(-/-) and C57BL/6 mice we used a higher dose of an attenuated variant of MHV-A59, C12. The attenuated variant induced less demyelination in C57BL/6 mice compared to wild type A59, but the levels observed were not significantly different from those seen in beta(2)M(-/-) mice. Thus, MHV-induced demyelination can occur in some animals in the absence of MHC class I and CD8(+) cells.