Influenza vaccine induces intracellular immune memory of human NK cells.

Influenza vaccine induces intracellular immune memory of human NK cells.
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DOI:
10.1371/journal.pone.0121258
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Wei H
Wei H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dou Y;Fu B;Sun R;Li W;Hu W;Tian Z;Wei H

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流感疫苗引发抗原特异性抗体和免疫记忆,以保护人类免受漂移变体的感染。然而,什么支持或限制了疫苗的有效性和持续时间尚不清楚。在这里,我们接种健康志愿者与每年的疫苗配方,并研究了动态的T细胞,自然杀伤(NK)细胞和抗体反应后,再刺激与异源或同源流感病毒株。流感疫苗诱导潜在的记忆NK细胞,在前6个月内增加抗原特异性回忆IFN-γ应答。在其他NK细胞标志物(CD 45 RO、NKp 44、CXCR 6、CD 57、NKG 2C、CCR 7、CD 62 L和CD 27)不存在显著变化的情况下,流感疫苗诱导具有细胞内NKp 46表达的独特特征的记忆NK细胞。事实上,表面NKp 46被内化,并且NKp 46(细胞内)+CD 56 dim NK细胞的动态增加与疫苗接种后流感病毒再刺激的IFN-γ产生增加正相关。此外,抗NKp 46抗体阻断IFN-γ应答。这些发现为疫苗诱导免疫和NK相关疾病的新机制提供了见解,这可能有助于未来设计持久和通用的疫苗。
Influenza vaccines elicit antigen-specific antibodies and immune memory to protect humans from infection with drift variants. However, what supports or limits vaccine efficacy and duration is unclear. Here, we vaccinated healthy volunteers with annual vaccine formulations and investigated the dynamics of T cell, natural killer (NK) cell and antibody responses upon restimulation with heterologous or homologous influenza virus strains. Influenza vaccines induced potential memory NK cells with increased antigen-specific recall IFN-γ responses during the first 6 months. In the absence of significant changes in other NK cell markers (CD45RO, NKp44, CXCR6, CD57, NKG2C, CCR7, CD62L and CD27), influenza vaccines induced memory NK cells with the distinct feature of intracellular NKp46 expression. Indeed, surface NKp46 was internalized, and the dynamic increase in NKp46(intracellular)+CD56dim NK cells positively correlated with increased IFN-γ production to influenza virus restimulation after vaccination. In addition, anti-NKp46 antibodies blocked IFN-γ responses. These findings provide insights into a novel mechanism underlying vaccine-induced immunity and NK-related diseases, which may help to design persisting and universal vaccines in the future.
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