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：（改编自研究者摘要）大量HIV 被困在滤泡树突状细胞（FDC）的生发中心， 次级淋巴组织 当CD+4 T细胞 持续下降，这些带有病毒负载FDC的生殖中心， 活化的CD+4 T细胞和高细胞活化状态是 艾滋病毒活跃复制的主要场所。 研究人员假设， FDC通过以下方式在HIV发病机制中发挥主要作用：（1）作为HIV的储存库， 感染性HIV;（2）加强新进入的新生感染和 细胞和潜伏感染的细胞进入生殖中心;和 (3)通过在存在高水平的中和抗体的情况下允许感染， 抗体的 他们还假设FDC促进感染的特征 可能会被抑制。 为了支持这一假设，他们 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。 他们也有证据表明，FDC促进了 新感染和感染艾滋病毒的人数均显着增加 潜伏感染的T细胞 最后，他们发现FDC允许感染 即使在中和抗体大量过量的情况下。 研究人员认为，他们的假设令人兴奋， 了解FDC对HIV发病机制的贡献将是至关重要的， 设计干预策略， 传染性病毒 目前阻止病毒复制的策略 靶向FDC储库，其保留直到细胞被破坏， 淋巴结在艾滋病发病前就已退化。 因此， FDC的贡献可能使他们能够成功地瞄准这一重要细胞 和它的病毒库