In vivo and in vitro models of demyelinating diseases XXIV. The infectious process in cyclosporin A treated Wistar Lewis rats inoculated with JHM virus()

Zimmer, Mitchell J.; Dales, Samuel

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(6) 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.