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Rapid Expansion of Virus-Specific CD4(+) T Cell Types in the CNS of Susceptible Mice Infected with Theiler s Virus #MMPMID33086489
Kang HS; Hou W; Kim BS
Int J Mol Sci 2020[Oct]; 21 (20): ? PMID33086489show ga
The infection of susceptible mice with Theiler's murine encephalomyelitis virus (TMEV) induces a T cell-mediated demyelinating disease. This system has been studied as a relevant infection model for multiple sclerosis (MS). Therefore, defining the type of T cell responses and their functions is critically important for understanding the relevant pathogenic mechanisms. In this study, we adoptively transferred naive VP2-specific TCR-Tg CD4(+) T cells into syngeneic susceptible SJL mice and monitored the development of the disease and the activation and proliferation of CD4(+) T cells during the early stages of viral infection. The preexisting VP2-specific naive CD4(+) T cells promoted the pathogenesis of the disease in a dose-dependent manner. The transferred VP2-specific CD4(+) T cells proliferated rapidly in the CNS starting at 2-3 dpi. High levels of FoxP3(+)CD4(+) T cells were found in the CNS early in viral infection (3 dpi) and persisted throughout the infection. Activated VP2-specific FoxP3(+)CD4(+) T cells inhibited the production of IFN-gamma, but not IL-17, via the same VP2-specific CD4(+) T cells without interfering in proliferation. Thus, the early presence of regulatory T cells in the CNS with viral infection may favor the induction of pathogenic Th17 cells over protective Th1 cells in susceptible mice, thereby establishing the pathogenesis of virus-induced demyelinating disease.
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Int+J+Mol+Sci 2020 ; 21 (20): ?
