IMPACT OF ART ON DC & TREG RESPONSES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们假设在致病性SIV感染的早期阶段（在显著的免疫损伤之前）开始的ART对口腔免疫功能的影响很小（如果有的话）。这将与未经治疗的SIV感染形成对比，其中口腔（和全身）免疫功能最终被破坏。具体而言，我们认为未经治疗的SIV感染将阻碍先天DC（和EC）功能，以促进TcB的扩张，并进一步抑制控制口腔病原体所需的效应子反应。我们相信，接受抗逆转录病毒治疗的感染动物的基本口服免疫功能将与未感染动物（有或无抗逆转录病毒治疗）的基本口服免疫功能相当。评价连续ART对口腔黏膜固有和获得性免疫应答的影响。18只印度雄性恒河猴被纳入研究。用2000 TCID 50的wtSIVmac 239在扁桃体上攻击12只动物。 SIV攻击后2周开始ART，允许初始病毒扩增。未感染的动物平行接受ART。ART方案包括与PMPA（20 mg/kg/d s.c.）和FTC（40 mg/kg/d s.c.）。总共给药34周。SIV感染和ART治疗的动物保持正常的口腔和全身免疫功能，具有较低的病毒设定点。 然而，在SIV感染的ART未治疗的动物中观察到免疫系统的显著破坏、疾病进展和高得多的病毒设定点。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We hypothesized that ART initiated during the early stages of pathogenic SIV infection (prior to significant immune damage) will have little, if any, impact on oral immune function. This will contrast untreated SIV infection in which oral (and systemic) immune functions are ultimately destroyed. Specifically, we propose that untreated SIV infection will impede innate DC (and EC) functions to favor the expansion of Tregs and further dampen effector responses needed to control oral pathogens. We believe that basic oral immune function in infected animals receiving ART will be comparable to that seen in uninfected animals (with or without ART). To evaluate the effect of continuous ART on innate and adaptive oral mucosal immune responses. 18 Indian male rhesus monkeys were included in the study. 12 animals were challenged with 2000 TCID50 of wtSIVmac239 on the tonsils. ART was commenced 2 weeks after SIV challenge allowing initial virus expansion. Uninfected animals received ART in parallel. ART regimen involved combined treatment with PMPA (20 mg/kg/d s.c.) and FTC (40 mg/kg/d s.c.). This was given for 34 weeks in total. The SIV infected and ART treated animals maintained normal oral and systemic immune functions with lower viral set point. Whereas, significant destruction of the immune system, disease progression, and much higher viral set points were observed the SIV infected ART untreated animals.