MECHANISMS OF SIV SUPPRESSION BY CD8+ LYMPHOCYTES

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。 一些观察结果表明，CD 8 + T细胞控制HIV和SIV感染期间的病毒复制。然而，这种抗病毒作用的机制仍然知之甚少。在最近的研究（Klatt，PloS Pathogens 2010）中，我们发现，在早期和晚期SIV感染中，CD 8+淋巴细胞的消耗不改变感染细胞的体内寿命，因此表明由CD 8+淋巴细胞介导的SIV抑制可能涉及直接的细胞溶解效应以及非细胞溶解机制。目前的项目于2010年8月获得资助，将包括体内CD 8+淋巴细胞耗竭实验，旨在更好地阐明这些细胞在RMs慢性SIV感染期间的抗病毒作用。我们目前正处于该提案的四个目标中的两个中提出的CD 8消耗的复杂体内实验的规划阶段，其中总共15个健康RM将首先用SIVmac感染，然后在慢性感染的早期阶段（即，在已经达到病毒设定点之后）消耗CD 8。将通过组织学、流式细胞术和病毒学试验分析一些关键的免疫学和病毒学标志物。我们最近确定了足够数量的动物，这些动物已被隔离并分配到研究中。因此，我们将很快开始拟议的实验，并将在生成相关结果时对其进行分析。我们相信，这些实验将提供重要的见解CD 8+淋巴细胞抑制病毒复制在SIV感染。

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. Several observations indicate that CD8+ T cells control virus replication during HIV and SIV infection. However, the mechanisms underlying this antiviral effect are still poorly understood. In a recent study (Klatt, PloS Pathogens 2010), we found that, in both early and late SIV infection, depletion of CD8+ lymphocytes does not change the vivo lifespan of infected cell, thus indicating that SIV suppression mediate by CD8+ lymphocytes may involve direct cytolythic effects as well as non-cytolythic mechanisms. The current project, funded in August 2010, will include experiments of in vivo CD8+ lymphocyte depletion aimed at better elucidating the antiviral effects of these cells during chronic SIV infection of RMs. We are currently in the planning phase of the complex in vivo experiments of CD8 depletion proposed in two of the four Aims of this proposal, in which a total of 15 healthy RM will be first infected with SIVmac and then CD8 depleted during the early stages of chronic infection (I.e. after the viral set point has been reached). A number of key immunological and virological markers will be analyzed by histology, flow cytometry, and virological assays. We recently identified the sufficient number of animals that have been already been placed under quarantine and assigned to the study. As such, we will soon start the proposed experiment, and the relevant results will be analyzed as they are generated. We believe that these experiments will provide important insights into CD8+ lymphocyte inhibition of virus replication during SIV infection.