The role of CD8+ T cells and major histocompatibility complex class I expression in the central nervous system of mice infected with neurovirulent Sindbis virus
The role of CD8+ T cells and major histocompatibility complex class I expression in the central nervous system of mice infected with neurovirulent Sindbis virus
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DOI：
10.1128/jvi.74.13.6117-6125.2000
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发表时间：
2000-07-01
影响因子：
5.4
通讯作者：
Griffin, DE
中科院分区：
文献类型：
--
作者：
Kimura, T;Griffin, DE
在神经毒性辛德毕斯病毒（NSV）诱导的脑炎中，浸润神经实质的CD 8（+）T细胞的作用知之甚少，NSV优先感染小鼠脑和脊髓中的神经元;然而，人们普遍认为神经元可以表达很少的（如果有的话）主要组织相容性复合体（MHC）I类分子。我们研究了CD 8（+）T细胞在NSV脑炎中的可能作用和相互作用，证实NSV脑内接种后，内皮细胞、炎性细胞和室管膜细胞上均表达MHC I类抗原（H2K/D），神经元上未见免疫反应。另一方面，在原位杂交与探针的MHC I类重链，β 2微球蛋白，和TAP 1和TAP 2的mRNA显示在大多数的神经元，以及在炎症细胞，内皮细胞，室管膜细胞在感染小鼠的中枢神经系统的表达增加。NSV感染的神经元可能由于转录后阻断而不能表达MHC I类分子，或者可能仅表达非经典的MHC I类基因。为了更好地理解CD 8（+）T细胞在NSV诱导的致死性脑炎中的作用，研究了缺乏功能性CD 8（+）T细胞的小鼠。CD 8的存在或不存在并不改变结果，但β 2微球蛋白的缺乏改善了存活率。有趣的是，在免疫活性小鼠中病毒RNA的细胞内水平比在没有功能性CD 8（+）T细胞的小鼠中下降得更快。这些观察结果表明，CD 8（+）T细胞可能间接地起作用，可能通过细胞因子，有助于清除神经元中的病毒RNA。
Little is known about the role of CD8(+) T cells infiltrating the neural parenchyma during encephalitis induced by neurovirulent Sindbis virus (NSV), NSV preferentially infects neurons in the mouse brain and spinal cord; however, it is generally accepted that neurons can express few if any major histocompatibility complex (MHC) class I molecules. We evaluated the possible roles and interactions of CD8(+) T cells during NSV encephalitis and demonstrated that MHC class I antigen (H2K/D) was expressed on endothelial cells, inflammatory cells, and ependymal cells after intracerebral inoculation of NSV, No immunoreactivity was observed in neurons. On the other hand, in situ hybridization with probes for MHC class I heavy chain, beta 2 microglobulin, and TAP1 and TAP2 mRNAs revealed increased expression in a majority of neurons, as well as in inflammatory cells, endothelial cells, and ependymal cells in the central nervous system of infected mice. NSV-infected neurons may fail to express MHC class I molecules due to a posttranscriptional block or may express only nonclassical MHC class I genes. To better understand the role CD8(+) T cells play during fatal encephalitis induced by NSV, mice lacking functional CD8(+) T cells were studied. The presence or absence of CD8 did not alter outcome, but absence of beta 2 microglobulin improved survival, Interestingly, the intracellular levels of viral RNA decreased more rapidly in immunocompetent mice than in mice without functional CD8(+) T cells, These observations suggest that CD8(+) T cells may act indirectly, possibly via cytokines, to contribute to the clearance of viral RNA in neurons.