NK Cells as Effectors of Acquired Immune Responses: Effector CD4+ T Cell-Dependent Activation of NK Cells Following Vaccination
NK Cells as Effectors of Acquired Immune Responses: Effector CD4+ T Cell-Dependent Activation of NK Cells Following Vaccination
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DOI：
10.4049/jimmunol.1000844
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发表时间：
2010-09-01
影响因子：
4.4
通讯作者：
Riley, Eleanor M.
中科院分区：
文献类型：
--
作者：
Horowitz, Amir;Behrens, Ron H.;Riley, Eleanor M.
我们描述了疫苗诱导的幼年成年志愿者对狂犬病毒的细胞反应。与目前的模式相反，我们观察到，在接种疫苗的个体（而非未接种疫苗的个体）中，灭活狂犬病病毒再刺激pbmc后，体外NK细胞细胞因子的产生和脱颗粒反应有效且持续时间长。这种“召回”NK细胞反应完全依赖于来自CD45RO(+) CD4(+) T细胞的ag特异性IL-2以及来自辅助细胞的IL-12和IL-18。重要的是，在病毒再次攻击后的最初12-18小时内，NK细胞占所有ifn - γ分泌和脱粒细胞的70%以上，这表明它们可能需要在疫苗接种后快速控制感染。NK细胞的活化可能是il -2分泌效应记忆T细胞的关键功能。虽然之前已经报道过il -2依赖性接种后NK细胞活化，但这是第一次认识到这种效应的大小及其对疫苗诱导的整体反应的贡献，并且已经阐明了接种后NK活化的机制。我们的数据将允许评估疫苗诱导免疫的标准方案适用于评估NK细胞效应反应。免疫学杂志，2010,18(5):2808-2818。
We characterized vaccine-induced cellular responses to rabies virus in naive adult volunteers. Contrary to current paradigms, we observed potent and prolonged in vitro NK cell cytokine production and degranulation responses after restimulation of PBMCs with inactivated rabies virus in vaccinated, but not in unvaccinated, individuals. This "recall" NK cell response was absolutely dependent on Ag-specific IL-2 from CD45RO(+) CD4(+) T cells as well as IL-12 and IL-18 from accessory cells. Importantly, NK cells represented over 70% of all IFN-gamma-secreting and degranulating cells in the first 12-18 h after virus rechallenge indicating they may be required for rapid control of infection after vaccination. Activation of NK cells may be a critical function of IL-2-secreting effector memory T cells. Although IL-2-dependent postvaccination NK cell activation has been reported previously, this is the first time the magnitude of this effect and its contribution to the overall vaccine-induced response has been appreciated and the mechanisms of NK activation postvaccination have been elucidated. Our data will allow standard protocols for evaluating vaccine-induced immunity to be adapted to assess NK cell effector responses. The Journal of Immunology, 2010, 185: 2808-2818.