IMMUNIZATION ACTIVATES TRANSIENT SIV VIRAL REPLICATION

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。 HIV感染会导致CD4T细胞免疫的质和量的丧失。抗逆转录病毒疗法(ART)恢复了CD4T细胞对许多常见病原体的反应，但HIV特异性反应仍然不足。同样，接受抗逆转录病毒治疗的慢性感染受试者用艾滋病毒抗原进行治疗性免疫会导致较差的艾滋病毒特异性反应。在这项研究中，我们使用了HIV感染者在慢性感染期间接受ART治疗的猕猴模型，以研究免疫后早期SIV抗原刺激在淋巴结中的后果。用SIVmac251慢性感染巨细胞病毒Mamu A*01阳性恒河猴，并接受抗逆转录病毒治疗。分析引流淋巴结和外周血中SIV Gag和CMV pp65抗原免疫后的免疫和病毒应答。免疫动物一侧为SIV Gag编码基因，对侧为CMV pp65编码基因，可同时从同一动物身上获得两种抗原的引流淋巴结，以供直接比较。我们观察到，SIV和CMV抗原免疫都能刺激侧方淋巴结的免疫激活和一过性抗原特异性T细胞反应。CMV特异性反应在免疫后50天内持续有效，而SIV特异性反应是短暂的，很快消失。SIV抗原刺激可在引流淋巴结诱导一过性SIV病毒复制。我们假设，对SIV抗原刺激反应的病毒复制限制了SIV抗原特异性反应的产生，这表明在HIV感染者中观察到的早期丢失和较差的HIV特异性CD4T细胞反应的机制。

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. HIV infection causes a qualitative and quantitative loss of CD4+ T cell immunity. The institution of anti-retroviral therapy (ART) restores CD4+ T cell responses to many common pathogens, but HIV-specific responses remain deficient. Similarly, therapeutic immunization with HIV antigens of chronically infected ART treated subjects results in poor HIV-specific responses. In this study, we used a macaque model of HIV-infected individuals treated with ART during chronic infection to study the consequences of SIV antigen stimulation in lymph nodes early after immunization. CMV seropositive Mamu A*01 positive rhesus macaques were chronically infected with SIVmac251 and treated with ART. The immune and viral responses to SIV gag and CMV pp65 antigen immunization in draining lymph nodes and peripheral blood was analyzed. Animals were immunized with SIV gag encoding plasmid on one side and CMV pp65 encoding plasmid on the contralateral side, which allowed draining lymph nodes for each antigen to be obtained at the same time from the same animal for direct comparison. We observed that both SIV and CMV antigen immunizations stimulated immune activation and transient antigen-specific T cell responses in inpsilateral lymph nodes. The CMV-specific responses were potent and sustained in the periphery for 50 days post-immunization, while the SIV-specific responses were transient and extinguished quickly. The SIV antigen stimulation induced transient SIV viral replication in the draining lymph nodes. We hypothesize that viral replication in response to SIV antigen stimulation limits the generation of SIV antigen-specific responses, suggesting a mechanism for the early loss and poor HIV-specific CD4+ T cell response observed in HIV-infected individuals.