MONOCYTE/MACROPHAGES IN PEDIATRIC AIDS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 与感染艾滋病毒的成年人相比，感染艾滋病毒的儿童通常病毒载量更高，病情进展更快。人们普遍认为，在感染HIV-1的成人和儿童中，CD4+T细胞的破坏是导致免疫缺陷的主要原因。巨噬细胞是先天免疫系统的重要细胞成分，是连接先天免疫和获得性免疫的纽带，也是HIV/SIV感染的重要靶点。在这里，我们建议证明，除了CD4+T细胞外，单核/巨噬细胞也与HIV感染儿童快速发展为艾滋病密切相关。我们最近发现，与组织巨噬细胞的死亡相关的外周血单核细胞的大量更新与艾滋病的进展相关，并且是比CD4+T细胞下降更好地预测成年猕猴艾滋病进展的标志。我们的初步研究还表明，与感染SIV的成年猴子相比，所有感染SIV的儿童猴子在感染后不久都观察到非常均匀的高单核细胞周转率。这一周转率与艾滋病晚期成年感染猴子的观察结果相当。我们的假设是，SIV对组织巨噬细胞的大量早期损伤是可能解释儿童艾滋病快速进展机制的缺失环节。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Children infected with HIV, in contrast to infected adults, often have higher virus loads and progress to AIDS faster. It is widely accepted that destruction of CD4+ T cells is the primary cause of immunodeficiency in HIV-1 infected adults and children. Macrophages, important cell components of the innate immune system and link between innate and adaptive immunity, are also important targets of HIV/SIV infection. Here, we propose to demonstrate that, in addition to the CD4+ T cells, monocytes/macrophages are also heavily involved in the rapid progression to AIDS in HIV infected children. We have recently shown that the massive turnover of peripheral monocytes associated with death of tissue macrophages correlates with AIDS progression and is a better predictive marker for AIDS progression in adult macaques than CD4+ T cell decline. Our preliminary study also showed that in contrast to adult SIV infected monkeys, a very homogeneous high monocyte turnover was observed in all SIV-infected pediatric monkeys soon after infection. This turnover rate was equivalent to that observed in the adult infected monkeys in the terminal stages of AIDS. Our hypothesis is that massive early damage of tissue macrophages by SIV is the missing link that may explain the mechanism of rapid progression in pediatric AIDS.