FOLLICULAR DENDRITIC CELLS AND HIV PATHOGENESIS

滤泡树突细胞和 HIV 发病机制

• 批准号: 2442700
• 负责人: Gregory F. Burton
• 金额: $ 23.86万
• 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 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2442700
• 关键词: HIV infections; antibody receptor; apoptosis; complement receptor; dendritic cells; human immunodeficiency virus; human tissue; laboratory mouse; microorganism immunology; neutralizing antibody; polymerase chain reaction; tissue /cell culture; virus infection mechanism; zidovudine

DESCRIPTION: (Adapted from investigator's abstract) Large amounts of HIV are trapped on follicular dendritic cells (FDC) in the germinal centers of secondary lymphoid tissues. throughout clinical latency when CD+4 T cells continually decline, these germinal centers with virus-laden FDC, highly activated, CD+4 T cells and a state of high cellular activation are the primary sites of active HIV replication. The investigators hypothesize that FDC play a major role in HIv pathogenesis by: (1) serving as a reservoir of infectious HIV; (2) potentiating both de novo infection of newly entering cells and of latently infected cells coming into the germinal center; and (3) by permitting infection in the presence of high levels of neutralizing antibody. They also hypothesize that FDC features that promote infection may be able to be inhibited. In support of the hypothesis, they have recently shown that FDC trapped HIV immune complexes are highly infectious and they have data suggesting that FDC maintain HIV infectivity even in the absence of viral replication. They also have evidence that FDC promote a significant increase in the amount of HIV infection in both newly and latently infected T cells. Lastly they have found that FDC permit infection even in the presence of a vast excess of neutralizing antibody. The investigators believe that their hypothesis is exciting and that an understanding of FDC contributions to HIV pathogenesis will be critical in designing intervention strategies that can attack this reservoir of infectious virus. Current strategies to stop viral replication do not target the FDC reservoir which remains until the cells are destroyed and the lymph node involutes prior to the onset of AIDS. thus an understanding of FDC contributions may allow them to successfully target this important cell and its viral reservoir.

描述：（改编自研究者的摘要）大量艾滋病毒 被捕获在生发中心的滤泡树突状细胞（FDC）上 次级淋巴组织。 CD+4 T 细胞在整个临床潜伏期 不断下降，这些带有病毒的 FDC 的生发中心，高度 激活的 CD+4 T 细胞和高度细胞激活状态是 HIV 活跃复制的主要位点。 研究人员假设 FDC 通过以下方式在 HIV 发病机制中发挥重要作用：(1) 作为病毒储存库 传染性艾滋病毒； (2) 加强新入境者的从头感染 细胞和潜伏感染细胞进入生发中心；和 (3) 在存在高水平中和性的情况下允许感染 抗体。 他们还假设 FDC 具有促进感染的功能 或许能够被抑制。 为了支持这个假设，他们有 最近表明，FDC 捕获的 HIV 免疫复合物具有高度传染性 他们有数据表明，FDC 即使在 没有病毒复制。 他们还有证据表明 FDC 提倡 艾滋病病毒感染者数量显着增加 潜伏感染的T细胞。 最后他们发现FDC允许感染 即使存在大量的中和抗体。 研究人员相信他们的假设是令人兴奋的 了解 FDC 对 HIV 发病机制的贡献对于以下方面至关重要 设计可以攻击这个水库的干预策略 传染性病毒。 目前阻止病毒复制的策略并不能 靶向 FDC 储存库，该储存库一直存在直至细胞被破坏并且 艾滋病发病前淋巴结退化。 从而了解 FDC 的贡献可能使他们能够成功地瞄准这个重要的细胞 及其病毒库。