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新发现：NK细胞是抗病毒T细胞的变阻器
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NK细胞担当抗病毒T细胞的变阻器
一直以来，抗病毒T细胞（Antiviral T cells）被认为能够调控HCV和HIV病毒入侵从而控制病毒的感染，无症状的持续感染或者严重的疾病，但迄今为止，引起这些结果的原因还不清楚。
最近，美国和德国科学家共同研究发现，NK细胞在人体内担当抗病毒T细胞的变阻器。近期的遗传学证据描述了一些NK细胞受体和HIV和HCV感染进程的相互关系，暗示NK细胞可能在T细胞相关疾病中扮演重要角色。尽管，NK细胞直接介导的溶解被病毒入侵的细胞可能有助于抵抗某些病毒的感染——特别是小鼠MCMV感染和人类HIV——NK细胞同样被怀疑具有免疫调节的功能。例如，NK细胞可能间接的调控T细胞响应来溶解被MCMV感染的APC。和MCMV相比，小鼠LCMV感染过程似乎会受到NK细胞的直接抗病毒性抵抗。我们检测了LCMV入侵小鼠时，NK细胞在调控T细胞依赖的病毒持续性感染和免疫病理学中所扮演的角色，确定了一个HIV和HCV入侵人体的模型（图1）。
Fig.1 Proposed model connecting NK-cell killing of CD4 T cell to CD8 T cells and infection outcome in the presence of NK cells
我们描述了一个三途径（Three-way）的相互作用，如何激活NK细胞溶解消除CD4 T细胞从而影响CD8 T细胞的功能和衰竭。当病毒为高剂量时，NK细胞通过使T细胞衰竭和病毒持续感染而避免宿主死亡，但是当病毒为中剂量时，NK细胞反而促进致命的T细胞介导的病理过程（NK cells paradoxically facilitated lethal T-cell-mediated pathology）。因此，作者认为，NK细胞扮演变阻器的角色，通过调控CD4 T细胞介导的支持抗病毒的CD8 T细胞来调控病毒性发病和病毒性持续感染。
Natural killer cells act as rheostats modulating antiviral T cells
Antiviral T cells are thought to regulate whether hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections result in viral control, asymptomatic persistence or severe disease, although the reasons for these different outcomes remain unclear. Recent genetic evidence, however, has indicated a correlation between certain natural killer (NK)-cell receptors and progression of both HIV and HCV infection, implying that NK cells have a role in these T-cell associated diseases. Although direct NK-cell-mediated lysis of virusinfected cells may contribute to antiviral defence during some virus infections—especially murine cytomegalovirus (MCMV) infections in mice and perhaps HIV in humans—NK cells have also been suspected of having immunoregulatory functions. For instance, NK cells may indirectly regulate T-cell responses by lysing MCMV-infected antigen-presenting cells. In contrast to MCMV, lymphocytic choriomeningitis virus (LCMV) infection in mice seems to be resistant to any direct antiviral effects of NK cells. Here we examine the roles of NK cells in regulating T-cell-dependent viral persistence and immunopathology in mice infected with LCMV, an established model for HIV and HCV infections in humans. We describe a three-way interaction, whereby activated NK cells cytolytically eliminate activated CD4 T cells that affect CD8 T-cell function and exhaustion. At high virus doses, NK cells prevented fatal pathology while enabling T-cell exhaustion and viral persistence, but at medium doses NK cells paradoxically facilitated lethal T-cell-mediated pathology. Thus, NKcells can act as rheostats, regulating CD4 T-cell-mediated support for the antiviralCD8Tcells that control viral pathogenesis and persistence.
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原文下载：http://changlab.ucsd.edu/immunology/Documents/Waggoner%20et%20al%20Nature%202011.pdf
https://blog.sciencenet.cn/blog-553053-530834.html
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