ROLE OF VIRUS SPECIFIC IMMUNITY IN PRIMATE MODELS

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。 该项目研究了通过单独施用IL-12或与IL-2或IL-15组合施用IL-12以及使用PMPA的结构化抗病毒化疗中断方案来促进细胞介导的免疫应答以恢复/增强SIV感染后的抗病毒免疫应答的细胞因子的潜力。过去一年主要致力于监测感染SIVmac251并接受STI和IL-12治疗的恒河猴。对具有可变水平的免疫介导的SIV病毒血症控制的存活猴进行IL-15的长期给药，随后进行IL-7的长期给药，以记录这些T细胞定向的细胞因子对体内病毒载量和抗病毒免疫应答的影响。此外，平行研究中启动的mangabey试图描绘T细胞功能障碍的致病性恒河猴与非致病性mangabey猴。在两种模型中纵向研究了调节性T细胞的作用以及PD-1表达对CD4和CD8 + T细胞的潜在作用。此外，结合流感免疫接种，对中枢记忆和效应记忆T细胞特异性钾通道抑制剂的体内给药进行初步评价。 该项目已接近完成，目前正在观察最后四只动物的长期治疗效果。

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. This project investigates the potential for cytokines promoting cell mediated immune responses for restoring/augmenting antiviral immune responses following SIV infection by administration of IL-12 alone or in combination with IL-2 or Il-15 and a structured antiviral chemotherapy interruption protocol using PMPA. The past year has been devoted primarily to the monitoring of the rhesus infected with SIVmac251 and treated with STI and IL-12. Surviving monkeys with variable levels of immune mediated control of the SIV viremia have been subjected to chronic administration of IL-15 followed by IL-7 to document the effect of these T cell directed cytokines on the viral loads and antiviral immune responses in vivo. In addition, parallel studies were initiated in sooty mangabeys in attempt to delineate T cell dysfunction in the pathogenic rhesus vs non pathogenic mangabey monkey. The role of regulatory T cells was investigated longitudinally in both models as well as the potential role of PD-1 expression on CD4 and CD8+ T cells. In addition, a preliminary evaluation of the in vivo administration of inhibitors of potassium channels specific for central memory and effector memory T cells was performed in conjunction with an immunization with influenza. The project is near its completion and the final four animals are being observed for longterm effects of the therapy.