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Imunoresponse against Human herpesvirus-6 and Human herpesvirus-7

针对人类疱疹病毒 6 和人类疱疹病毒 7 的免疫反应

基本信息

批准号：
14570264
负责人：
YOSHIDA Mariko
金额：
$ 2.24万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570264/
关键词：
HHV-6 HHV-7 Plasmacytoid dendritic cells IFN-alpha Immune response Cord Blood Mononuclear cells

项目摘要

Plasmacytoid dendritic cell (DC) precursors in human blood are now recognized as identical to natural alpha interferon (IFN-α)-producing cells (IPCs) and are thought to play an important role in antiviral immunity. Therefore, We tried to investigate the susceptibility as well as the cellular responses of DCs to two variants of human herpesvirus 6 (HHV-6), namely A and B, and human herpesvirus 7 (HHV-7). DCs are isolated from cord blood mononuclear ells (CBMCs) by magnetic-bead separation. Although HHV-6A, HHV-6B and HHV-7 are Closely related in DNA sequence, each has distinctive genomic, antigenic, and biological properties. First, DCs are infected with these viruses at various multiplicity of infection and examined by Facs for defection of surface antigen, by ELISA for production of cytokines, and by the transmission electron microscopy (TEM) for replication of the viruses. Based on the observation of TEM, all of these viruses infect DCs and produce progeny viruses. The reticular incl … More usion bodies with a skein-like appearance were commonly observed, which are the particular structure in the nuclei of infected cells with these viruses. In the expression of surface antigens, CD80, CD83, CD86, and HLA-DR, which are marker antigen for maturation of DCs, are determined on infected cells with HHV-6 more intensive than on HHV-7 infected cells. Both of HHV-6A and HHV-6B infections trigger DCs to produce vast amounts of IFN-α and induces DCs to differentiate into mature DCs. In contrast, DCs infected with HHV-7 do not produce IFN-α neither differentiate into mature DCs. Second, naive CD4^+ T cells obtained from CBMCs are co-cultured with virus-infected DCs and measured the CD4^+ T cells-induced cytokines. HHV-6B infected DCs stimulate naive CD4^+ T cells to produce IFN-γ and interleukin-10 (IL-10). HHV-6A or HHV-7 infected DCs stimulate naive CD4^+_T cells to produce IL-4, IL-5, IL-10, and IFN-γ. These findings suggest that producing large amount or IFN-α from infected DCs dose not contribute to a critical link between innate and adaptive immunity. Viral specific proteins may be an important role on the differentiation of DCs and on the following events to dictate T cell mediated immunity. Less

人类血液中的浆细胞样树突状细胞（DC）前体现在被认为与天然α干扰素（IFN-α）产生细胞（IPCs）相同，并被认为在抗病毒免疫中发挥重要作用。因此，我们试图研究dc对人类疱疹病毒6 （HHV-6）的两种变体（A和B）和人类疱疹病毒7 （HHV-7）的易感性和细胞反应。采用磁珠分离技术从脐带血单核细胞（CBMCs）中分离出DCs。虽然HHV-6A、HHV-6B和HHV-7在DNA序列上密切相关，但它们各自具有不同的基因组、抗原和生物学特性。首先，dc以不同的感染方式感染这些病毒，并通过Facs检测表面抗原的缺陷，通过ELISA检测细胞因子的产生，以及通过透射电子显微镜（TEM）检测病毒的复制。通过透射电镜观察，这些病毒都能感染树突状病毒并产生子代病毒。在感染病毒细胞的细胞核中，通常观察到更多的束状融合体，这是病毒感染细胞的特殊结构。表面抗原CD80、CD83、CD86和HLA-DR作为dc成熟的标记抗原，在HHV-6感染细胞上的表达比在HHV-7感染细胞上的表达更强烈。HHV-6A和HHV-6B感染均可触发dc产生大量IFN-α，诱导dc向成熟dc分化。相比之下，感染HHV-7的dc不能产生IFN-α，也不能分化为成熟的dc。其次，从cbmc中获得的初始CD4^+ T细胞与病毒感染的dc共培养，并测量CD4^+ T细胞诱导的细胞因子。HHV-6B感染的dc刺激初始CD4^+ T细胞产生IFN-γ和白细胞介素-10 （IL-10）。HHV-6A或HHV-7感染的dc刺激初始CD4^+_T细胞产生IL-4、IL-5、IL-10和IFN-γ。这些发现表明，从感染的dc中产生大量IFN-α并不是先天免疫和适应性免疫之间的关键联系。病毒特异性蛋白可能在dc分化和以下事件中起重要作用，从而决定T细胞介导的免疫。少