Cytotoxic T Cells Are the Predominant Players Providing Cross-Protective Immunity Induced by γ-Irradiated Influenza A Viruses
Cytotoxic T Cells Are the Predominant Players Providing Cross-Protective Immunity Induced by γ-Irradiated Influenza A Viruses
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DOI：
10.1128/jvi.02508-09
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发表时间：
2010-05-01
影响因子：
5.4
通讯作者：
Alsharifi, Mohammed
中科院分区：
文献类型：
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作者：
Furuya, Yoichi;Chan, Jennifer;Alsharifi, Mohammed
我们之前证明，单剂量的无佐剂鼻内伽马射线照射的甲型流感病毒可以为小鼠提供针对同源和异亚型攻击的强大保护，包括 H5N1 禽病毒株的攻击。我们研究了观察到的交叉保护背后的机制，以确定适应性免疫反应的哪些部分参与介导这种保护。对基因敲除小鼠的研究表明，交叉保护性免疫主要由 T 细胞介导，并依赖于细胞溶解效应分子穿孔素。来自免疫小鼠的记忆 T 细胞（而非记忆 B 细胞）的过继转移，可以保护首次接受者免受致命的异亚型流感病毒的攻击。此外，伽马射线照射的流感病毒诱导交叉反应性 Tc 细胞反应，但不诱导交叉中和或交叉保护抗体。此外，组织学分析显示，与未接种疫苗的对照组相比，异亚型攻击后接种疫苗的小鼠肺部炎症有所减轻。这种炎症的减轻与T细胞（CD4+和CD8+）的早期募集增强以及早期流感病毒特异性细胞毒性T细胞反应有关。因此，接种伽马射线照射的甲型流感病毒疫苗诱导的交叉保护性免疫主要是由 Tc 细胞反应介导的。
We previously demonstrated that a single dose of nonadjuvanted intranasal gamma-irradiated influenza A virus can provide robust protection in mice against both homologous and heterosubtypic challenges, including challenge with an H5N1 avian virus strain. We investigated the mechanism behind the observed cross-protection to define which arms of the adaptive immune response are involved in mediating this protection. Studies with gene knockout mice showed the cross-protective immunity to be mediated mainly by T cells and to be dependent on the cytolytic effector molecule perforin. Adoptive transfer of memory T cells from immunized mice, but not of memory B cells, protected naive recipients against lethal heterosubtypic influenza virus challenge. Furthermore, gamma-irradiated influenza viruses induced cross-reactive Tc-cell responses but not cross-neutralizing or cross-protective antibodies. In addition, histological analysis showed reduced lung inflammation in vaccinated mice compared to that in unvaccinated controls following heterosubtypic challenge. This reduced inflammation was associated with enhanced early recruitment of T cells, both CD4(+) and CD8(+), and with early influenza virus-specific cytotoxic T-cell responses. Therefore, cross-protective immunity induced by vaccination with gamma-irradiated influenza A virus is mediated mainly by Tc-cell responses.