Zimmer M J, Dales S
Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
Microb Pathog. 1989 Jan;6(1):7-16. doi: 10.1016/0882-4010(89)90003-x.
In the present study we investigated age related effects of inoculum size and cellular immunity on the CNS disease caused by JHM virus (JHMV) in Wistar Lewis (WL) rats. Onset of resistance normally becomes evident by the 10th day when inoculation is made with 10(5) pfu or less. The resistance could be abrogated in 15 day old animals by increasing the dose two-fold, but with rare exceptions, in 35 day old rats an 80-fold increase in pfu fails to surmount resistance. However, treatment with the immunosuppressant drug cyclosporin A (CsA) abolished resistance, whereby rats challenged at 35 days of age were susceptible to JHMV. The histopathological evidence and disease symptoms in the CsA treated group resembled closely those observed in our previous study with athymic, nude rats. Microscopic examination of the CNS from untreated, infected rats revealed extensive inflammatory responses characterized by perivascular cuffing and mononuclear infiltrates into the neuropile. The parallel CsA treated group showed that inflammatory responses of this type in the CNS were either minimal or absent. From the present evidence, we conclude that JHMV infection, which involves both neuronal and oligodendrocytic elements, is kept in check by the cellular immune system. When cellular immunity is suppressed or absent the disease process is altered from one in which white matter demyelination predominates to another form of disease in which neuronal involvement is prominent.
在本研究中，我们调查了接种量和细胞免疫与年龄相关的效应，这些效应会影响Wistar Lewis（WL）大鼠中由JHM病毒（JHMV）引起的中枢神经系统疾病。当接种10⁵个噬斑形成单位（pfu）或更少时，通常在第10天开始出现抵抗力。通过将剂量增加两倍，可以消除15日龄动物的抵抗力，但在35日龄大鼠中，除了极少数例外，pfu增加80倍也无法克服抵抗力。然而，用免疫抑制药物环孢素A（CsA）进行治疗可消除抵抗力，从而使35日龄时受到攻击的大鼠对JHMV易感。CsA治疗组的组织病理学证据和疾病症状与我们之前对无胸腺裸鼠的研究中观察到的情况非常相似。对未治疗的感染大鼠的中枢神经系统进行显微镜检查发现，广泛的炎症反应表现为血管周围套袖状浸润和单核细胞浸润到神经纤维网中。平行的CsA治疗组表明，中枢神经系统中这种类型的炎症反应要么最小化，要么不存在。根据目前的证据，我们得出结论，涉及神经元和少突胶质细胞成分的JHMV感染受到细胞免疫系统的控制。当细胞免疫受到抑制或不存在时，疾病过程会从以白质脱髓鞘为主的一种形式转变为以神经元受累为主的另一种疾病形式。
