Stohlman S A, Bergmann C C, van der Veen R C, Hinton D R
Department of Neurology, USC School of Medicine, Los Angeles 90033.
J Virol. 1995 Feb;69(2):684-94. doi: 10.1128/JVI.69.2.684-694.1995.
Acute infection of the central nervous system by the neurotropic JHM strain of mouse hepatitis virus (JHMV) induces nucleocapsid protein specific cytotoxic T lymphocytes (CTL) not found in the periphery (S. Stohlman, S. Kyuwa, J. Polo, D. Brady, M. Lai, and C. Bergmann, J. Virol. 67:7050-7059, 1993). Peripheral induction of CTL specific for the nucleocapsid protein of JHMV by vaccination with recombinant vaccinia viruses was unable to provide significant protection to a subsequent lethal virus challenge. By contrast, the transfer of nucleoprotein-specific CTL protected mice from a subsequent lethal challenge by reducing virus replication within the central nervous system, demonstrating the importance of the CTL response to this epitope in JHMV infection. Transfer of these CTL directly into the central nervous system was at least 10-fold more effective than peripheral transfer. Histological analysis indicated that the CTL reduced virus replication in ependymal cells, astrocytes, and microglia. Although the CTL were relatively ineffective at reducing virus replication in oligodendroglia, survivors showed minimal evidence of virus persistence within the central nervous system and no evidence of chronic ongoing demyelination.
嗜神经小鼠肝炎病毒（JHMV）的JHM株对中枢神经系统的急性感染会诱导出在外周未发现的核衣壳蛋白特异性细胞毒性T淋巴细胞（CTL）（S.斯托尔曼、S.久和、J.波罗、D.布雷迪、M.赖和C.伯格曼，《病毒学杂志》67:7050 - 7059，1993年）。通过接种重组痘苗病毒对外周进行JHMV核衣壳蛋白特异性CTL的诱导，无法为后续的致死性病毒攻击提供显著保护。相比之下，核蛋白特异性CTL的转移通过减少中枢神经系统内的病毒复制，保护小鼠免受后续的致死性攻击，这证明了CTL对该表位的反应在JHMV感染中的重要性。将这些CTL直接转移到中枢神经系统比外周转移至少有效10倍。组织学分析表明，CTL减少了室管膜细胞、星形胶质细胞和小胶质细胞中的病毒复制。尽管CTL在减少少突胶质细胞中的病毒复制方面相对无效，但存活小鼠的中枢神经系统内几乎没有病毒持续存在的迹象，也没有慢性进行性脱髓鞘的迹象。
