MONOCYTE/MACROPHAGES IN PEDIATRIC AIDS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 与受感染的成年人相比，感染艾滋病毒的儿童往往病毒载量更高，发展为艾滋病的速度更快。人们普遍认为，CD 4 + T细胞的破坏是HIV-1感染成人和儿童免疫缺陷的主要原因。巨噬细胞是天然免疫系统的重要细胞成分，是天然免疫和获得性免疫之间的纽带，也是HIV/SIV感染的重要靶点。在这里，我们建议证明，除了CD 4 + T细胞，单核细胞/巨噬细胞也大量参与艾滋病毒感染的儿童迅速发展为艾滋病。我们最近发现，与组织巨噬细胞死亡相关的外周血单核细胞的大量周转与艾滋病进展相关，并且是成年猕猴中比CD 4 + T细胞下降更好的艾滋病进展预测标志物。我们的初步研究还表明，与成年SIV感染猴相比，在所有SIV感染的儿童猴中，在感染后不久观察到非常均一的高单核细胞更新。这一周转率相当于在艾滋病末期的成年受感染猴子中观察到的周转率。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科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.