Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help.
Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help.
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DOI：
10.1038/nature17979
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发表时间：
2016-05-26
期刊：
影响因子：
64.8
通讯作者：
Iwasaki A
中科院分区：
文献类型：
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作者：
Iijima N;Iwasaki A
循环抗体能够进入大多数组织，以介导对入侵病原体的监视和清除。免疫特权组织，如大脑和外周神经系统，分别被血脑屏障和血神经屏障与血浆蛋白隔离开来。然而，循环抗体必须以某种方式进入这些组织，才能发挥其抗菌功能。在此，我们研究了抗体进入神经组织以控制感染的机制。利用生殖器疱疹感染的小鼠模型，我们证明在远端部位免疫后，抗体和CD4 T细胞对于保护宿主都是必需的。我们发现记忆性CD4 T细胞在单纯疱疹病毒2型（HSV - 2）感染时迁移到背根神经节（DRG）和脊髓。一旦进入这些神经组织，CD4 T细胞分泌干扰素（IFN）-γ并介导局部血管通透性增加，使抗体能够进入以控制病毒。在鼻内接种水疱性口炎病毒后，也观察到抗体进入大脑需要CD4 T细胞的类似情况。我们的研究结果揭示了CD4辅助作用在将抗体动员到感染的外周部位以帮助限制病毒传播方面此前未被重视的作用。
Circulating antibodies can access most tissues to mediate surveillance and elimination of invading pathogens. Immunopriviledged tissues such as the brain and the peripheral nervous system, are shielded from plasma proteins, by the blood-brain barrier and blood nerve barrier, respectively. Yet, circulating antibodies must somehow gain access to these tissues in order to mediate their antimicrobial functions. Here, we examine the mechanism by which antibodies gain access to neuronal tissues to control infection. Using mouse model of genital herpes infection, we demonstrate that both antibodies and CD4 T cells are required to protect the host following immunization at a distal site. We show that memory CD4 T cells migrate to the dorsal root ganglia (DRG) and spinal cord in response to HSV-2 infection. Once inside these neuronal tissues, CD4 T cells secrete interferon (IFN)-γ and mediate local increase in vascular permeability, enabling antibody access for viral control. A similar requirement for CD4 T cells for antibody access to the brain was observed following intranasal challenge with vesicular stomatitis virus. Our results reveal a previously unappreciated role of CD4 help in mobilizing antibodies to the peripheral sites of infection where they help to limit viral spread.