TH17 CELLS IN AIDS PATHOGENESIS AND HIV VACCINES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心赠款提供。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。 为子项目列出的总成本可能 表示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。 Th 17细胞在人类和恒河猴（RM）的致病性HIV/SIV感染中优先耗尽，但在白眉猴（SM）的非致病性SIV感染中不优先耗尽。该项目的总体目标是阐明进行性和非进行性慢病毒感染中调节Th 17稳态的机制。在此期间，我们首先通过增加入组受试者的数量来扩展最初的观察结果，即HIV感染者的粘膜Th 17被耗尽。研究的这一部分现已完成，我们的人群包括28名艾滋病毒感染者和11名对照。更多的个体数量允许我们进行一些相关性。有趣的是，我们发现在HIV感染中，Th 17耗竭的严重程度与免疫激活水平相关，但与病毒载量无关。这些数据已纳入已发表的手稿（见出版物）。此外，我们开始了子目标#1c中详述的研究，其中6只RM已感染SIV，并将在慢性感染中接受抗逆转录病毒治疗（ART）。本研究将提供有关病毒复制受到抑制时Th 17重建的关键信息，以及ART中断后病毒反弹对Th 17的影响。此外，我们成功地鉴定了Th 17前体和产生Th 17分化细胞因子（如IL-21）的细胞，并且正在对SIV感染和未感染的非人灵长类动物中这些细胞的水平进行分析。

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. Th17 cells are preferentially depleted in pathogenic HIV/SIV infections of humans and rhesus macaques (RM), but not in nonpathogenic SIV infection of sooty mangabeys (SM). The overall aim of this project, funded 16 months ago, is to elucidate the mechanisms regulating Th17 homeostasis in progressive and nonprogressive lentiviral infections. In this period, we first expanded upon the original observation that mucosal Th17 are depleted in HIV-infected humans by increasing the numbers of enrolled subjects. This part of the study is now completed, with our population including 28 HIV-infected individuals and 11 controls. The higher numbers of individuals allowed us to perform a number of correlations. Interestingly, we found that in HIV infection the severity of Th17 depletion correlates with levels of immune activation, but not with viral load. These data have been included in a published manuscript (see publication). In addition, we started the study detailed in sub-Aim #1c in which six RM have been SIV infected and will be treated with antiretroviral therapy (ART) in the chronic infection. This study will provide key information on Th17 reconstitution when virus replication is suppressed, and on the effect on Th17 by the viral rebound that will follow ART interruption. Additionally, we successfully identified Th17 precursors and cells producing Th17-differentiating cytokine, such as IL-21, and the analyses of the levels of these cells in SIV infected and uninfected nonhuman primates are in progress.