HOMEOSTASIS OF CD4+ T CELLS IN NONHUMAN PRIMATES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 人类和恒河猴(RMS)的致病性HIV和SIV感染会导致进行性的CD4+T细胞耗尽和艾滋病。相比之下，非进展性SIV感染的煤质芒果鸟(SMS)的特征是保存了CD4+T细胞计数。目前，SMS和RMS维持CD4+T细胞内稳态的不同能力的机制尚不清楚。最近获奖的这项工作的范围是阐明这种不同表型的细胞和分子基础。具体目标包括识别体内抗体介导的CD4淋巴细胞耗尽后CD4+T细胞重建的物种特异性特征，以及一些在HIV/SIV感染背景下发挥关键作用的CD4+T细胞亚群的动态平衡调节的定义，如中央记忆、Th17、IL-21产生细胞。该项目于2010年9月获得资助，目前我们正处于目标1中包括的复合体内实验的规划阶段，其中6例健康的RM将接受抗CD4单抗的治疗。我们最近确定了已经被隔离的6只动物，现在被分配到这项研究中。因此，我们将很快开始拟议的治疗，旨在耗尽他们的CD4+细胞，然后纵向研究响应这种耗尽而增殖的CD4+T细胞的表型、功能和分子特征。

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.