TH17 CELLS IN AIDS PATHOGENESIS AND HIV VACCINES

TH17 细胞在艾滋病发病机制和 HIV 疫苗中的作用

• 批准号: 8357566
• 负责人: Mirko Paiardini
• 金额: $ 7.43万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357566
• 关键词: Acquired Immunodeficiency Syndrome; Cells; Cercocebus atys; Chronic; Data; Enrollment; Funding; Grant; HIV; HIV Infections; HIV vaccine; Homeostasis; Human; Individual; Infection; Interruption; Macaca mulatta; Manuscripts; National Center for Research Resources; Pathogenesis; Population; Primates; Principal Investigator; Publications; Publishing; Research; Research Infrastructure; Resources; SIV; Severities; Source; United States National Institutes of Health; Viral; Viral Load result; Virus Replication; antiretroviral therapy; cost; cytokine; immune activation; nonhuman primate; precursor cell; reconstitution

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 Th17 细胞在人类和恒河猴 (RM) 的致病性 HIV/SIV 感染中优先被耗尽，但在乌白眉猴 (SM) 的非致病性 SIV 感染中则不会。该项目于 16 个月前资助，其总体目标是阐明进行性和非进行性慢病毒感染中调节 Th17 稳态的机制。在此期间，我们首先通过增加招募受试者的数量，扩展了最初的观察结果，即感染 HIV 的人中粘膜 Th17 被耗尽。这部分研究现已完成，我们的人群包括 28 名 HIV 感染者和 11 名对照者。较多的个体数量使我们能够进行许多相关性分析。有趣的是，我们发现在 HIV 感染中，Th17 耗竭的严重程度与免疫激活水平相关，但与病毒载量无关。这些数据已包含在已发表的手稿中（参见出版物）。此外，我们开始了子目标#1c中详细介绍的研究，其中六名RM已感染SIV，并将在慢性感染中接受抗逆转录病毒疗法（ART）治疗。这项研究将提供有关病毒复制受到抑制时 Th17 重建以及 ART 中断后病毒反弹对 Th17 影响的关键信息。此外，我们成功鉴定了 Th17 前体和产生 Th17 分化细胞因子（例如 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。