HOMEOSTASIS OF CD4+ T CELLS IN NONHUMAN PRIMATES

非人灵长类动物 CD4 T 细胞的稳态

• 批准号: 8357565
• 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/8357565
• 关键词: Acquired Immunodeficiency Syndrome; Animals; Antibodies; Award; Biological Preservation; CD4 Positive T Lymphocytes; Cell Count; Cells; Cercocebus atys; Complex; Funding; Grant; HIV; Homeostasis; Human; Infection; Macaca mulatta; Mediating; Memory; Molecular; Molecular Profiling; Monoclonal Antibodies; National Center for Research Resources; Phase; Phenotype; Play; Primates; Principal Investigator; Proliferating; Quarantine; Regulation; Research; Research Infrastructure; Resources; Role; SIV; Source; T-Cell Depletion; T-Lymphocyte Subsets; United States National Institutes of Health; Work; base; cost; in vivo; nonhuman primate; reconstitution; research study; response

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. Pathogenic HIV and SIV infections of humans and Rhesus Macaques (RMs) result in progressive CD4+ T cell depletion and AIDS. In contrast, non-progressive SIV infection of sooty mangabeys (SMs) is characterized by preservation of CD4+ T cell counts. The mechanisms responsible for the differential ability to maintain CD4+ T cell homeostasis in SMs versus RMs are currently unknown. Scope of this recently awarded work is to elucidate the cellular and molecular basis for this divergent phenotype. Specific aims include the identification of species-specific features of CD4+ T cell reconstitution following antibody-mediated depletion of CD4 lymphocytes in vivo, and the definition of homeostatic regulation of a number of CD4+ T cell subsets that play a crucial role in the context of HIV/SIV infection, such as central memory, Th17, IL-21 producing cells. The project was funded in September 2010, and we are currently in the planning phase of the complex in vivo experiments included in Aim 1, in which 6 healthy RM will be treated with an anti-CD4 monoclonal antibody. We recently identified the 6 animals that have been already under quarantine and now assigned to the study. As such, we will soon start the proposed treatment aimed at depleting their CD4+ cells and then at investigating longitudinally the phenotypical, functional, and molecular profile of CD4+ T cells that proliferate in response to this depletion.

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。 人类和恒河猴 (RM) 的致病性 HIV 和 SIV 感染会导致 CD4+ T 细胞进行性耗竭和艾滋病。相比之下，乌白眉猴 (SM) 的非进行性 SIV 感染的特点是 CD4+ T 细胞计数保留。 SM 与 RM 中维持 CD4+ T 细胞稳态能力差异的机制目前尚不清楚。这项最近获奖的工作范围是阐明这种不同表型的细胞和分子基础。具体目标包括鉴定体内抗体介导的 CD4 淋巴细胞耗竭后 CD4+ T 细胞重建的物种特异性特征，以及定义在 HIV 背景下发挥关键作用的许多 CD4+ T 细胞亚群的稳态调节/SIV感染，如中枢记忆、Th17、IL-21产生细胞。该项目于 2010 年 9 月获得资助，目前正处于目标 1 中包含的复杂体内实验的规划阶段，其中将用抗 CD4 单克隆抗体治疗 6 名健康 RM。我们最近确定了 6 只已经被隔离并现在被分配到研究中的动物。因此，我们将很快开始拟议的治疗，旨在消除 CD4+ 细胞，然后纵向研究响应这种消除而增殖的 CD4+ T 细胞的表型、功能和分子特征。