| DA strain of Theiler's Murine Encephalomyelitis Virus (TMEV), a picornavirus, causes a biphasic disease in susceptible strain of mice. The disease is characterized by an early acute poliomyelitic disease of the gray matter followed by a late chronic primary demyelinating disease that strongly resembles the pathological changes seen in the white matter of patients suffering from multiple sclerosis (MS).; Although numerous reports have been made suggesting the importance of cytokines in the pathogenesis of TMEV-induced demyelination, a comprehensive evaluation depicting the possible role(s) cytokines play in demyelination has not been done. Our study shows that proinflammatory cytokine transcripts were found in the CNS of TMEV-infected mice at early acute (SJL and B6 mice) and late chronic demyelinating disease (only in SJL mice).; The presence of high levels of TGF-β in SJL mice during encephalomyelitis seem to suggest that the inability of SJL mice to completely clear the virus is due to a lack in sufficient cytotoxic activity while the absence of TGF-β in B6 during encephalomyelitis suggest that B6 mice are able to clear the virus. SJL mice undergo demyelinating disease that seems to involve both Th1 and Th2 cytokines as seen by the simultaneous appearance of both IL-2 and IL-4 prior to the demyelinating phase of TMEV-pathogenesis.; In contrast to B6 mice, FACS analysis revealed that, in addition to the early expression of TGF-β, SJL mice are unable to mount an efficient CD8+ T cell response. This is reflected (1) in the smaller number of CD8+ T cells infiltrating the CNS, (2) in the higher proportion of CD8+ T cells undergoing apoptosis, and (3) the higher proportion of CD8+ T cells expressing CTLA-4.; Lastly, we see that the suppression of the immune response by treatment with estrogen lead to an amelioration of the late chronic demyelinating disease without affecting encephalomyelitis. (Abstract shortened by UMI.)... |
