FOLLICULAR DENDRITIC CELLS & HIV PATHOGENESIS

描述(摘自申请者摘要)：FDC是一种罕见的易碎细胞 在淋巴结生发中心。它们可以将抗原保留在它们的母体中 在很长一段时间内，国家。私家侦探之前做了一个开创性的观察 FDC与中和剂混合后可保持HIV的传染性 抗体。基于这些观察，PI提出了一个假设，即FDDC 是感染艾滋病毒的危险的长期宿主，它们提供了 在体内对HIV致病机制的重要而独特的贡献 在没有病毒的情况下，将艾滋病毒以传染性形式维持多个月 复制，2)通过加强艾滋病毒感染/复制；以及3)通过允许 HIV在高浓度存在时对靶细胞的感染 中和抗体。 新提案的具体目标是： 1)建立FDC用来保护艾滋病毒不受损失的机制 传染性。 2)建立FDC用来加强艾滋病毒的机制 通过增加T细胞增殖和减少T细胞来感染/复制 细胞凋亡。 3)确定FDC在暴露于 艾滋病毒的突变者或新的种群。 4)确定FDC水库是否可以被摧毁。

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.