| Co-Investigator(Kenkyū-buntansha) |
INAMBA Hikaru Okayama University, Graduate School of Medicine and Dentristry, Assistant, 大学院・医歯学総合研究科, 助手 (20273972)
YAMADA Masao Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (40166731)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
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
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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
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