Imunoresponse against Human herpesvirus-6 and Human herpesvirus-7

人类血液中的树突状细胞(DC)前体细胞被认为与天然的干扰素(α)产生细胞相同，并被认为在抗病毒免疫中发挥重要作用。因此，我们试图研究树突状细胞对人类疱疹病毒6型(HHV-6)A、B和人类疱疹病毒7型(HHV-7)两种变异体的易感性和细胞反应。用磁珠分离法从脐血单个核细胞(CBMC)中分离出DC。虽然HHV-6A、HHV-6B和HHV-7在DNA序列上有密切的联系，但它们都具有不同的基因组、抗原性和生物学特性。首先，DC以不同的感染方式感染这些病毒，并通过流式细胞仪检测表面抗原的缺失，通过ELISA法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。根据透射电子显微镜观察，所有这些病毒都感染DC并产生子代病毒。含…的网状结构这些病毒感染细胞的细胞核中有特殊的结构，常可观察到较多的丝蛋白样小体。在表面抗原的表达中，CD80、CD83、CD86和人类白细胞抗原DR是DC成熟的标志抗原，在感染HHV-6的细胞上比在HHV-7感染的细胞上更强。HHV-6A和HHV-6B感染都会触发DC产生大量干扰素-α，并诱导DC分化为成熟的DC。相比之下，感染HHV-7的DC不产生干扰素-α，也不能分化为成熟的DC。其次，将从CBMCs中获得的初始CD4^+T细胞与感染病毒的DC共培养，检测CD4^+T细胞诱导的细胞因子。HHV-6B感染的树突状细胞刺激初始的CD4T细胞产生干扰素-γ和白介素10。HHV-6A或HHV-7感染的DC刺激初始的CD4T细胞产生IL-4、IL-5、IL-10和干扰素-γ。这些发现表明，从受感染的DC中产生大量的干扰素-α并不有助于天然免疫和获得性免疫之间的关键联系。病毒特异性蛋白可能在树突状细胞的分化和随后的调控T细胞免疫的事件中发挥重要作用。较少

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