FOLLICULAR DENDRITIC CELLS AND IMMUNOSUPPRESSION IN AIDS

滤泡树突状细胞（FDC）在免疫调节中起主要作用 最近被发现是艾滋病病毒的沉积地。 FDC服务 作为Ag的长期仓库，用于诱导和维持记忆 反应以及贡献Ag独立信号被认为是 是生发中心形成所必需的。 为了使Ag（或 感染性病原体）与FDC相关，无论是特异性Ab 和/或需要补体激活。 在这两者中的一个或两个之后 当事件发生时，免疫复合物或补体包被的颗粒被 形成并可以被捕获在FDC的树枝状表面上。 不久 在FDC上捕获后，发生锗酸盐中心形成。 这些德国人 中心由高度活化和快速增殖的B（和 CD 4 + T细胞。 在艾滋病毒感染中，病毒颗粒很快 与淋巴滤泡中的FDC相关，尽管其机制 该协会尚未成立。 一旦被困在FDC上，病毒 位于敏感细胞所在的生殖器中心区域 处于高度活跃的状态 因此，HIV在FDC上的定位显然 汇集了成功和成功所需的所有组件， 生产性感染的CD 4 + T细胞，并保持他们在一起，只要 FDC出席。 我们假设FDC凭借被困的艾滋病毒 和共刺激信号的产生起着至关重要的作用， 艾滋病的发病机制，并建议测试这两个在体内和在 体外模型 本提案的具体目标是：1）确定 HIV可以特异性地将自身靶向FDC，如果这种靶向是 通过补体激活、特异性Ab或其组合来完成 2）确定携带HIV的FDC是否可以直接感染活化的 CD 4 + T细胞，并评估HIV特异性抗体对此的贡献。 感染过程;和3）确定FDC和/或生发中心B 细胞可以提供足够的辅助细胞功能，以促进 静息CD 4 + T细胞的生产性感染。

Follicular dendritic cells (FDC) play a major role in immunoregulation and have recently been found to be a site of HIV deposition. FDC serve as long-term depots of Ag for induction and maintenance of anamnestic responses as well as contributing Ag independent signalling believed to be necessary for germinal center formation. In order for Ag (or infectious agents) to become associated with FDC, either specific Ab and/or complement activation is required. After one or both of these events have occurred, immune complexes or complement coated particles are formed and can be trapped on the dendritic surfaces of FDC. Shortly after trapping on FDC, germinal center formation occurs. These germinal centers are composed of highly activated and rapidly proliferating B (and CD4+ T) cells surrounding FDC. In HIV infection, viral particles quickly become associated with FDC in lymphoid follicles although the mechanism of this association has not been established. Once trapped on FDC, virus is localized to the germinal center area where susceptible cells reside in a highly activated state. Thus HIV localization on FDC apparently brings together all of the components needed for successful and productive infection of CD4 + T cells and keeps them together as long as the FDC are present. We hypothesize that FDC by virtue of trapped HIV and generation of costimulatory signals play a vital role In the pathogenesis of AIDS and propose to test this using both in vivo and in vitro models. The specific aims of this proposal are to: 1) determine if HIV can specifically target itself to FDC and if this targeting is accomplished by complement activation, specific Ab or a combination of both; 2) determine whether FDC bearing HIV can directly infect activated CD4 + T cells and to assess the contribution of HIV specific Ab on this infectious process; and 3) determine whether FDC and/or germinal center B cells can provide sufficient accessory cell function to promote productive infection of resting CD4 + T cells.