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.

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。 人类和恒河猴（RM）的病原性HIV和SIV感染导致进行性CD 4 + T细胞耗竭和AIDS。相比之下，乌白眉猴（SM）的非进行性SIV感染的特征是CD 4 + T细胞计数的保留。目前尚不清楚SM与RM中维持CD 4 + T细胞稳态的差异能力的机制。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。具体目标包括鉴定抗体介导的体内CD 4淋巴细胞耗竭后CD 4 + T细胞重建的种属特异性特征，以及定义在HIV/SIV感染背景下发挥关键作用的许多CD 4 + T细胞亚群的稳态调节，如中央记忆、Th 17、IL-21产生细胞。该项目于2010年9月获得资助，我们目前正处于目标1中所包括的复杂体内实验的规划阶段，其中6例健康RM将使用抗CD 4单克隆抗体进行治疗。我们最近确定了6只已经隔离的动物，现在分配到研究中。因此，我们将很快开始拟议的治疗，旨在耗尽他们的CD 4+细胞，然后纵向研究响应于这种耗尽而增殖的CD 4 + T细胞的表型，功能和分子特征。