Multiple sclerosis: autoimmunity and viruses.
Multiple sclerosis: autoimmunity and viruses.
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DOI：
10.1097/bor.0b013e328362004d
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发表时间：
2013-07
影响因子：
5.1
通讯作者：
Fujinami RS
中科院分区：
文献类型：
--
作者：
Cusick MF;Libbey JE;Fujinami RS
这篇综述将探讨病毒参与多发性硬化症发病机制的两个新方面。第一个方面是病毒之间复杂的相互作用。第二个方面是提出了一种机制，通过这种机制，自身反应性T细胞能够逃避胸腺选择，并可能识别自身和病原体。关于病毒，最近的研究表明，一种病毒可能会增强另一种病毒的复制，从而可能导致炎症和疾病进展的增加。此外，可能不复制的人类内源性逆转录病毒与某些疱疹病毒之间的相互作用也可能在疾病发病机制中发挥作用。从机制上讲，表达双重T细胞受体的T细胞将能够特异性地识别自身和外来抗原。因此，人类内源性逆转录病毒可能在多发性硬化症发病机制中发挥作用，并且多种病毒和具有双重T细胞受体的自身反应性CD8 + T细胞之间的相互作用可能在疾病的发病机制中发挥作用。中枢神经系统内或外周中的多种病毒感染与宿主对病毒感染的免疫应答之间的复杂相互作用可能是这样的，即多种病毒特异性导致识别自身并诱导多发性硬化症的T细胞的活化。因此，任何一种微生物都不太可能被确定为多发性硬化症的病原体，这反映在疾病的潜在触发机制的数量上。
This review will explore two new aspects of the involvement of viruses in multiple sclerosis pathogenesis. The first aspect is the complex interactions between viruses. The second aspect is the proposal of a mechanism by which autoreactive T cells are able to escape thymic selection and potentially recognize self and a pathogen. With regard to viruses, recent work has demonstrated that one virus may enhance the replication of another virus, potentially leading to an increase in inflammation and disease progression. Also, interactions between human endogenous retroviruses, which likely do not replicate, and certain herpes viruses, may also play a role in disease pathogenesis. Mechanistically, T cells expressing dual T-cell receptors would be able to recognize self and a foreign antigen specifically. Therefore, human endogenous retroviruses potentially play a role in multiple sclerosis pathogenesis, and both interactions between multiple viruses and autoreactive CD8+ T cells with dual T-cell receptors may play a role in the pathogenesis of the disease. The complex interactions between multiple viral infections, either within the central nervous system or in the periphery, and the host immune response to viral infection may be such that a variety of viral specificities result in the activation of T cells that recognize self and induce multiple sclerosis. Therefore, it is unlikely that any one microbe will be determined to be the causative agent of multiple sclerosis as reflected by the number of potential triggering mechanisms of the disease.