细胞毒性T淋巴细胞（CTL）突变体在小鼠肝炎病毒JHM株诱导的脱髓鞘中的作用

Role of CTL mutants in demyelination induced by mouse hepatitis virus, strain JHM.

作者信息

Perlman S, Pewe L

机构信息

Department of Pediatrics, University of Iowa, Iowa City 52242, USA.

出版信息

Adv Exp Med Biol. 1998;440:515-9. doi: 10.1007/978-1-4615-5331-1_66.

DOI:10.1007/978-1-4615-5331-1_66

PMID:9782323

Abstract

Mouse hepatitis virus, strain JHM (MHV-JHM) is a well described cause of demyelination. C57B1/6 (B6) mice infected at the suckling stage in the presence of protective antibodies remain asymptomatic initially but later develop clinical disease (hindlimb paralysis). Infectious virus can be isolated from these mice. Recently, two MHV-specific target epitopes for cytotoxic CD8 T cells have been identified in B6 mice. Our results show that in all mice with hindlimb paralysis, mutations can be detected in the RNA encoding the immunodominant of the two epitopes. These mutations result in a loss of recognition by MHV-specific cytotoxic T cells. These changes are not detected, for the most part, in mice that remain asymptomatic nor in mice with acute encephalitis. These results suggest that the development of CTL escape mutants is necessary for hindlimb paralysis to develop in this model.

摘要

小鼠肝炎病毒JHM株（MHV-JHM）是一种已被充分描述的脱髓鞘病因。在存在保护性抗体的情况下，哺乳期感染的C57B1/6（B6）小鼠最初无症状，但随后会发展为临床疾病（后肢麻痹）。可从这些小鼠中分离出传染性病毒。最近，在B6小鼠中鉴定出了两种细胞毒性CD8 T细胞的MHV特异性靶抗原表位。我们的结果表明，在所有出现后肢麻痹的小鼠中，编码这两种表位免疫显性表位的RNA中都能检测到突变。这些突变导致MHV特异性细胞毒性T细胞无法识别。在大部分无症状小鼠或急性脑炎小鼠中未检测到这些变化。这些结果表明，在该模型中，CTL逃逸突变体的产生是后肢麻痹发展所必需的。