CD8(+) T cell-mediated immune responses in West Nile virus (Sarafend strain) encephalitis are independent of gamma interferon.
2006
The flavivirus West Nile virus (WNV) can cause fatal encephalitis in humans and mice. It has recently been demonstrated, in an experimental model using WNV strain Sarafend and C57BL/6 mice, that both virus- and immune-mediated pathology is involved in WNV encephalitis, with CD8+ T cells being the dominant subpopulation of lymphocyte infiltrates in the brain. Here, the role of activated WNV-immune CD8+ T cells in mouse WNV encephalitis was investigated further. Passive transfer of WNV-immune CD8+ T cells reduced mortality significantly and prolonged survival times of mice infected with WNV. Early infiltration of WNV-immune CD8+ T cells into infected brains is shown, suggesting a beneficial contribution of these lymphocytes to recovery from encephalitis. This antiviral function was not markedly mediated by gamma interferon (IFN-γ), as a deficiency in IFN-γ did not affect mortality to two strains of WNV (Sarafend and Kunjin) or brain virus titres significantly. The cytolytic potential, as well as precursor frequency, of WNV-immune CD8+ T cells were not altered by the absence of IFN-γ. This was reflected in transfer experiments of WNV-immune CD8+ T cells from IFN-γ
−/− mice into WNV-infected wild-type mice, which showed that IFN-γ-deficient T cells were as effective as those from WNV-immune wild-type mice in ameliorating disease outcome. It is speculated here that one of the pleiotropic functions of IFN-γ is mimicked by WNV-Sarafend-mediated upregulation of cell-surface expression of major histocompatibility complex antigens, which may explain the lack of phenotype of IFN-γ
−/− mice in response to WNV.
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