IMPACT OF ART ON DC & TREG RESPONSES

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。 该研究的目的是评估连续ART对先天性和适应性外周和粘膜免疫应答的影响，并确定PolyIC是否可以增强ART治疗动物的口服免疫力。将2000 TCID^50的野生型SIVmac 239应用于12只动物的扁桃体，其中10只被感染。将这10只感染动物和8只未感染动物分为ART组和无ART组。尽管接受ART的所有动物的初始血浆病毒浓度峰值下降得更快，但有2只动物在ART下没有控制病毒。扁桃体的PolyICLC治疗被用作评价ART下口服免疫功能的工具。在感染的急性期（第2周），PDC的频率增加，在血液中观察到效应记忆CD 4 +T细胞的频率增加和CD 4+中枢记忆T细胞的百分比降低。从长期来看（第28周），我们发现两组之间没有显著差异。在polyICLC应用后，我们立即检测到所有组中MDC上的CD 80上调（第二次和第四次处理后）。在polyICLC应用后，所有组中Foxp 3 +Treg似乎也随时间增加。在第26、34、51周和尸检时间点，通过四色（TNF/IL-2/IFN γ/IL-17）细胞内细胞因子染色检测SIV和白色念珠菌特异性CD 4+和CD 8 + T细胞应答。与SIV+ART+相比，SIV+ART-组中产生TNF γ和IFN γ的SIV特异性CD 4+和CD 8 + T细胞应答更强，但未达到统计学显著性。在PolyICLC应用后，似乎还存在血小板特异性CD 4 + T细胞应答的降低（所有细胞因子）。首次应用PolyICLC后，在18只动物中的9只动物的口腔拭子中检测到CXCL 10水平升高。

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. The purpose of the study was to evaluate the effect of continuous ART on innate and adaptive peripheral and mucosal immune responses and determine whether PolyIC can boost oral immunity in ART-treated animals. 2000 TCID^50 of wild type SIVmac239 was applied to the tonsils of 12 animals, 10 of which became infected. These 10 infected animals and the 8 uninfected animals were divided into the ART vs no ART groups. Despite the initial peak plasma viremias decreasing more rapidly in all animals of the ART-receiving group, 2 animals did not control virus under ART. PolyICLC treatment of the tonsils was being used as a tool to evaluate oral immune function under ART. During the acute phase of infection (week 2), increased frequency of PDCs, increased frequency of effector memory CD4+T cells and decreased percentages of CD4+ central memory T cells were observed in the blood. Chronically (at week 28) we found no significant differences between the groups. Immediately, after polyICLC application, we detected an up-regulation of CD80 on MDC in all groups (after the second and fourth treatments). There also appeared to be an increase of Foxp3+Treg over time in all groups following the polyICLC applications. SIV and Candida albicans-specific CD4+ and CD8+ T cell responses were detected by 4-color (TNF/IL-2/IFN gamma/IL-17) intracellular cytokine staining at weeks 26, 34, 51 and at the time point of necropsy. TNFgamma and IFN gamma-producing SIV-specific CD4+ and CD8+ T cell responses were stronger in SIV+ART- group compared to SIV+ART+ but did not reach statistical significance. There also appeared to be a decrease of Candida-specific CD4+ T cell responses after PolyICLC application (all cytokines). Increased levels of CXCL10 were detected in oral swabs in 9 out of 18 animals after the first PolyICLC application.