FOLLICULAR DENDRITIC CELLS & HIV PATHOGENESIS

滤泡树突状细胞

• 批准号: 6214687
• 负责人: Gregory F. Burton
• 金额: $ 28.89万
• 依托单位: BRIGHAM YOUNG UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-15 至 2001-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6214687
• 关键词: HIV envelope protein gp120; HIV infections; apoptosis; dendritic cells; human immunodeficiency virus; human tissue; laboratory mouse; latent virus infection; lymph nodes; lymphocyte proliferation; microorganism immunology; nucleic acid sequence; polymerase chain reaction; tissue /cell culture; virus infection mechanism; virus receptors; virus replication

Description (from applicant's abstract): FDC are rare and fragile cells located in germinal centers of lymph nodes. They can retain antigens in their native state for an extended period. The PI previously made a seminal observation that FDC preserves the infectiousness of HIV when mixed with neutralizing antibodies. Based on these observations, the PI presents a hypothesis that FDCs are a dangerous long-term reservoir of infectious HIV and that they provide important and unique contributions to HIV pathogenesis 1) by in vivo maintenance of HIV in an infectious form for many months without viral replication, 2) by potentiating HIV infection/replication; and 3) by permitting HIV infection of target cells in the presence of high concentrations of neutralizing antibody. Specific aims for the new proposal are: 1) To establish the mechanisms used by FDC to protect HIV from the loss of infectivity. 2) To establish the mechanisms used by FDC to potentiate HIV infection/replication by increasing T cell proliferation and by reducing T cell apoptosis. 3) To determine if FDC can archive infectious HIV while being exposed to mutants or new populations of HIV. 4) To determine if the FDC reservoir can be destroyed.

描述（来自申请人摘要）：FDC是一种罕见且脆弱的细胞，位于 在淋巴结的生发中心。它们可以将抗原保留在它们的天然 国家延长一段时间。PI之前做了一个开创性的观察， FDC在与中和剂混合时保留了HIV的传染性 抗体的基于这些观察，PI提出了一个假设，即FDCs 是一个危险的传染性艾滋病病毒的长期储存库， 重要和独特的贡献艾滋病毒发病机制1）通过在体内 维持HIV感染状态数月而无病毒感染 复制，2）通过增强HIV感染/复制;和3）通过允许 HIV感染的靶细胞中存在高浓度的 中和抗体 新提案的具体目标是： 1)建立FDC使用的机制，以保护艾滋病毒免受 传染性 2)建立FDC用于增强HIV的机制 通过增加T细胞增殖和通过减少T细胞增殖， 凋亡 3)确定FDC在暴露于以下物质时是否可以存档传染性HIV： 突变体或新的艾滋病毒种群。 4)以确定FDC储药器是否可被破坏。