Wang Yang, Lobigs Mario, Lee Eva, Koskinen Aulikki, Müllbacher Arno
Division of Immunology and Genetics, The John Curtin School of Medical Research, The Australian National University (ANU), PO Box 334, Canberra, ACT 2601, Australia.
J Gen Virol. 2006 Dec;87(Pt 12):3599-3609. doi: 10.1099/vir.0.81306-0.
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-gamma), as a deficiency in IFN-gamma 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-gamma. This was reflected in transfer experiments of WNV-immune CD8(+) T cells from IFN-gamma(-/-) mice into WNV-infected wild-type mice, which showed that IFN-gamma-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-gamma 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-gamma(-/-) mice in response to WNV.
黄病毒属的西尼罗河病毒（WNV）可在人类和小鼠中引发致命性脑炎。最近，在一项使用WNV萨拉芬德株和C57BL/6小鼠的实验模型中证实，病毒介导的病理过程和免疫介导的病理过程均参与了WNV脑炎，其中CD8(+) T细胞是脑内淋巴细胞浸润的主要亚群。在此，对活化的WNV免疫CD8(+) T细胞在小鼠WNV脑炎中的作用进行了进一步研究。被动转移WNV免疫CD8(+) T细胞可显著降低死亡率，并延长感染WNV小鼠的存活时间。研究显示WNV免疫CD8(+) T细胞可早期浸润至受感染的脑内，提示这些淋巴细胞对脑炎恢复有有益作用。这种抗病毒功能并非由γ干扰素（IFN-γ）显著介导，因为IFN-γ缺陷对两种WNV毒株（萨拉芬德株和库京株）的死亡率或脑内病毒滴度均无显著影响。IFN-γ缺失并未改变WNV免疫CD8(+) T细胞的细胞溶解潜能以及前体细胞频率。这在将IFN-γ(-/-)小鼠的WNV免疫CD8(+) T细胞转移至感染WNV的野生型小鼠的实验中得到体现，结果表明缺乏IFN-γ的T细胞在改善疾病转归方面与WNV免疫野生型小鼠的T细胞效果相同。据推测，WNV-萨拉芬德介导的主要组织相容性复合体抗原细胞表面表达上调模拟了IFN-γ的多效性功能之一，这可能解释了IFN-γ(-/-)小鼠对WNV无反应的表型。
