Axonal damage is T cell mediated and occurs concomitantly with demyelination in mice infected with a neurotropic coronavirus
Axonal damage is T cell mediated and occurs concomitantly with demyelination in mice infected with a neurotropic coronavirus
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DOI：
10.1128/jvi.75.13.6115-6120.2001
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发表时间：
2001-07-01
影响因子：
5.4
通讯作者：
Perlman, S
中科院分区：
文献类型：
--
作者：
Dandekar, AA;Wu, CF;Perlman, S
感染小鼠肝炎病毒（MHV）株JHM的小鼠发生原发性脱髓鞘。在这里，我们表明，轴突损伤发生在脱髓鞘的地区，也在邻近地区没有髓鞘损伤。免疫缺陷MHV感染的RAG 1-/-小鼠（重组酶激活基因1表达缺陷的小鼠）不发生脱髓鞘，除非它们接受来自先前针对MHV免疫的小鼠的脾细胞（G. F. Wu，中国茶条A.丹德卡尔湖Pewe和S. Perlman，J. Immunol，165：2278-2286，2000）。在本研究中，我们发现，过继性T细胞转移也需要在这些动物中观察到的大多数轴突损伤，脱髓鞘和轴突损伤在转移后7天都很明显。最近的数据表明，轴突损伤是在多发性硬化症患者中观察到的长期残疾的主要因素。我们的数据表明，免疫系统介导的轴突损伤也是MHV诱导的脱髓鞘小鼠的常见特征。值得注意的是，似乎有一个最小的，如果有的话，脱髓鞘和轴突损伤的外观之间的时间间隔。
Mice infected with mouse hepatitis virus (MHV) strain JHM develop primary demyelination. Herein we show that axonal damage occurred in areas of demyelination and also in adjacent areas devoid of myelin damage. Immunodeficient MHV-infected RAG1-/- mice (mice defective in recombinase activating gene 1 expression) do not develop demyelination unless they receive splenocytes from a mouse previously immunized against MHV (G. F. Wu, A. Dandekar, L. Pewe, and S. Perlman, J. Immunol, 165:2278-2286, 2000). In the present study, we show that adoptive transfer of T cells was also required for the majority of the axonal injury observed in these animals, Both demyelination and axonal damage were apparent by 7 days posttransfer. Recent data suggest that axonal injury is a major factor in the long-term disability observed in patients with multiple sclerosis, Our data demonstrate that immune system-mediated damage to axons is also a common feature in mice with MHV induced demyelination. Remarkably, there appeared to be a minimal, if any, interval of time between the appearance of demyelination and that of axonal injury.