Division of Infectious Diseases, University of Pennsylvania, Philadelphia, PA, USA.
Retrovirology. 2011 Jul 13;8:57. doi: 10.1186/1742-4690-8-57.
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 pathogens, but HIV-specific responses remain deficient. Similarly, therapeutic immunization with HIV antigens of chronically infected, ART treated subjects results in poor induction of HIV-specific CD4 responses. In this study, we used a macaque model of ART treatment during chronic infection to study the virologic consequences of SIV antigen stimulation in lymph nodes early after immunization. Rhesus CMV (RhCMV) 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 RhCMV pp65 antigen immunization in draining lymph nodes and peripheral blood were analyzed. Animals were immunized on contralateral sides with SIV gag and RhCMV pp65 encoding plasmids, which allowed lymph nodes draining each antigen to be obtained at the same time from the same animal for direct comparison.
We observed that both SIV and RhCMV immunizations stimulated transient antigen-specific T cell responses in draining lymph nodes. The RhCMV-specific responses were potent and sustained (50 days post-immunization) in the periphery, while the SIV-specific responses were transient and extinguished quickly. The SIV antigen stimulation selectively induced transient SIV replication in draining lymph nodes.
The data are consistent with a model whereby viral replication in response to SIV antigen stimulation limits the generation of SIV antigen-specific responses and suggests a potential mechanism for the early loss and poor HIV-specific CD4+ T cell response observed in HIV-infected individuals.
HIV 感染导致 CD4+T 细胞免疫的定性和定量丧失。抗逆转录病毒疗法（ART）的实施恢复了 CD4+T 细胞对许多病原体的反应，但 HIV 特异性反应仍然不足。同样，对接受 ART 治疗的慢性感染患者用 HIV 抗原进行治疗性免疫接种，导致 HIV 特异性 CD4 反应的诱导很差。在这项研究中，我们使用了慢性感染期间接受 ART 治疗的猕猴模型，研究了免疫接种后早期淋巴结中 SIV 抗原刺激的病毒学后果。恒河猴 CMV（RhCMV）血清阳性、Mamu A*01 阳性的恒河猴被 SIVmac251 慢性感染，并接受 ART 治疗。分析了引流淋巴结和外周血中 SIV gag 和 RhCMV pp65 抗原免疫接种的免疫和病毒反应。动物在对侧用 SIV gag 和 RhCMV pp65 编码质粒免疫接种，这允许从同一动物同时获得引流每种抗原的淋巴结，以便直接比较。
我们观察到，SIV 和 RhCMV 免疫接种都刺激了引流淋巴结中短暂的抗原特异性 T 细胞反应。RhCMV 特异性反应在周围具有强大和持久的作用（免疫后 50 天），而 SIV 特异性反应是短暂的，并迅速消失。SIV 抗原刺激选择性地诱导了引流淋巴结中的 SIV 复制。
数据与以下模型一致，即 SIV 抗原刺激引起的病毒复制限制了 SIV 抗原特异性反应的产生，并提示了在 HIV 感染个体中观察到的 HIV 特异性 CD4+T 细胞反应早期丧失和不佳的潜在机制。
