在先天性淋巴细胞性脉络丛脑膜炎病毒感染的新生大鼠模型中,t细胞是部分但不是全部小脑病理的基础

H. Klein, Glenda K. Rabe, B. Karacay, D. Bonthius
{"title":"在先天性淋巴细胞性脉络丛脑膜炎病毒感染的新生大鼠模型中,t细胞是部分但不是全部小脑病理的基础","authors":"H. Klein, Glenda K. Rabe, B. Karacay, D. Bonthius","doi":"10.1093/jnen/nlw079","DOIUrl":null,"url":null,"abstract":"Lymphocytic choriomeningitis virus (LCMV) infection during pregnancy injures the human fetal brain. Neonatal rats inoculated with LCMV are an excellent model of congenital LCMV infection because they develop cerebellar injuries similar to those in humans. To evaluate the role of T-lymphocytes in LCMV-induced cerebellar pathology, congenitally athymic rats, deficient in T-lymphocytes were compared with euthymic rats. Peak viral titers and cellular targets of infection were similar, but viral clearance from astrocytes was impaired in the athymic rats. Cytokines and chemokines rose to higher levels and for a greater duration in the euthymic rats than in their athymic counterparts. The euthymic rats developed an intense lymphocytic infiltration, accompanied by destructive lesions of the cerebellum and a neuronal migration defect because of T-cell-mediated alteration of Bergmann glia. These pathologic changes were absent in the athymic rats but were restored by adoptive transfer of lymphocytes. Athymic rats were not free of pathologic effects, however, as the virus induced cerebellar hypoplasia. Thus, T-lymphocytes play key roles in LCMV clearance, cytokine/chemokine responses, and pathogenesis of destructive lesions and neuronal migration disturbances but not all pathology is T-lymphocyte-dependent. Cerebellar hypoplasia from LCMV occurs even in the absence of T-lymphocytes and is likely due to the viral infection itself.","PeriodicalId":16434,"journal":{"name":"Journal of Neuropathology & Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":"{\"title\":\"T-Cells Underlie Some but Not All of the Cerebellar Pathology in a Neonatal Rat Model of Congenital Lymphocytic Choriomeningitis Virus Infection\",\"authors\":\"H. Klein, Glenda K. Rabe, B. Karacay, D. Bonthius\",\"doi\":\"10.1093/jnen/nlw079\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Lymphocytic choriomeningitis virus (LCMV) infection during pregnancy injures the human fetal brain. Neonatal rats inoculated with LCMV are an excellent model of congenital LCMV infection because they develop cerebellar injuries similar to those in humans. To evaluate the role of T-lymphocytes in LCMV-induced cerebellar pathology, congenitally athymic rats, deficient in T-lymphocytes were compared with euthymic rats. Peak viral titers and cellular targets of infection were similar, but viral clearance from astrocytes was impaired in the athymic rats. Cytokines and chemokines rose to higher levels and for a greater duration in the euthymic rats than in their athymic counterparts. The euthymic rats developed an intense lymphocytic infiltration, accompanied by destructive lesions of the cerebellum and a neuronal migration defect because of T-cell-mediated alteration of Bergmann glia. These pathologic changes were absent in the athymic rats but were restored by adoptive transfer of lymphocytes. Athymic rats were not free of pathologic effects, however, as the virus induced cerebellar hypoplasia. Thus, T-lymphocytes play key roles in LCMV clearance, cytokine/chemokine responses, and pathogenesis of destructive lesions and neuronal migration disturbances but not all pathology is T-lymphocyte-dependent. Cerebellar hypoplasia from LCMV occurs even in the absence of T-lymphocytes and is likely due to the viral infection itself.\",\"PeriodicalId\":16434,\"journal\":{\"name\":\"Journal of Neuropathology & Experimental Neurology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2016-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neuropathology & Experimental Neurology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/jnen/nlw079\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neuropathology & Experimental Neurology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/jnen/nlw079","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 3

摘要

妊娠期淋巴细胞性脉络丛脑膜炎病毒(LCMV)感染会损伤人类胎儿的大脑。接种LCMV的新生大鼠是先天性LCMV感染的良好模型,因为它们的小脑损伤与人类相似。为了探讨t淋巴细胞在lcmv诱导的小脑病理中的作用,我们将t淋巴细胞缺乏的先天性胸腺大鼠与正常胸腺大鼠进行了比较。病毒滴度峰值和感染的细胞靶点相似,但在胸腺大鼠中星形胶质细胞的病毒清除受损。细胞因子和趋化因子在健康大鼠中上升到更高的水平,持续时间也更长。健康大鼠出现强烈的淋巴细胞浸润,伴有小脑的破坏性病变和由于t细胞介导的伯格曼胶质细胞改变而导致的神经元迁移缺陷。这些病理变化在胸腺大鼠中不存在,但通过过继性淋巴细胞转移可以恢复。然而,由于病毒引起的小脑发育不全,胸腺发育不全的大鼠并非没有病理影响。因此,t淋巴细胞在LCMV清除、细胞因子/趋化因子反应、破坏性病变和神经元迁移障碍的发病机制中发挥关键作用,但并非所有病理都依赖t淋巴细胞。LCMV引起的小脑发育不全即使在没有t淋巴细胞的情况下也会发生,这可能是由病毒感染本身引起的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
T-Cells Underlie Some but Not All of the Cerebellar Pathology in a Neonatal Rat Model of Congenital Lymphocytic Choriomeningitis Virus Infection
Lymphocytic choriomeningitis virus (LCMV) infection during pregnancy injures the human fetal brain. Neonatal rats inoculated with LCMV are an excellent model of congenital LCMV infection because they develop cerebellar injuries similar to those in humans. To evaluate the role of T-lymphocytes in LCMV-induced cerebellar pathology, congenitally athymic rats, deficient in T-lymphocytes were compared with euthymic rats. Peak viral titers and cellular targets of infection were similar, but viral clearance from astrocytes was impaired in the athymic rats. Cytokines and chemokines rose to higher levels and for a greater duration in the euthymic rats than in their athymic counterparts. The euthymic rats developed an intense lymphocytic infiltration, accompanied by destructive lesions of the cerebellum and a neuronal migration defect because of T-cell-mediated alteration of Bergmann glia. These pathologic changes were absent in the athymic rats but were restored by adoptive transfer of lymphocytes. Athymic rats were not free of pathologic effects, however, as the virus induced cerebellar hypoplasia. Thus, T-lymphocytes play key roles in LCMV clearance, cytokine/chemokine responses, and pathogenesis of destructive lesions and neuronal migration disturbances but not all pathology is T-lymphocyte-dependent. Cerebellar hypoplasia from LCMV occurs even in the absence of T-lymphocytes and is likely due to the viral infection itself.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信