The functional properties of circulating CD8+ T cells have been associated with immune control of HIV. However, viral replication occurs predominantly in secondary lymphoid tissues, such as lymph nodes (LNs). We used an integrated single-cell approach to characterize effective HIV-specific CD8+ T cell responses in the LNs of elite controllers (ECs), defined as individuals who suppress viral replication in the absence of antiretroviral therapy (ART). Higher frequencies of total memory and follicle-homing HIV-specific CD8+ T cells were detected in the LNs of ECs compared with the LNs of chronic progressors (CPs) who were not receiving ART. Moreover, HIV-specific CD8+ T cells potently suppressed viral replication without demonstrable cytolytic activity in the LNs of ECs, which harbored substantially lower amounts of CD4+ T cell-associated HIV DNA and RNA compared with the LNs of CPs. Single-cell RNA sequencing analyses further revealed a distinct transcriptional signature among HIV-specific CD8+ T cells from the LNs of ECs, typified by the down-regulation of inhibitory receptors and cytolytic molecules and the up-regulation of multiple cytokines, predicted secreted factors, and components of the protein translation machinery. Collectively, these results provide a mechanistic framework to expedite the identification of novel antiviral factors, highlighting a potential role for the localized deployment of noncytolytic functions as a determinant of immune efficacy against HIV.

中文翻译：

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HIV 的精英控制与淋巴组织 CD8+ T 细胞的独特功能和转录特征相关。


循环 CD8+ T 细胞的功能特性与 HIV 的免疫控制有关。然而，病毒复制主要发生在次级淋巴组织，例如淋巴结（LN）。我们使用集成的单细胞方法来表征精英控制者 (EC) 的 LN 中有效的 HIV 特异性 CD8+ T 细胞反应，精英控制者定义为在缺乏抗逆转录病毒治疗 (ART) 的情况下抑制病毒复制的个体。与未接受 ART 的慢性进展者 (CP) 的淋巴结相比，在 EC 的淋巴结中检测到更高频率的总记忆和滤泡归巢 HIV 特异性 CD8+ T 细胞。此外，HIV特异性CD8+T细胞在EC的LN中有效抑制病毒复制，但没有明显的细胞溶解活性，与CP的LN相比，EC的LN中CD4+T细胞相关的HIV DNA和RNA的含量显着降低。单细胞RNA测序分析进一步揭示了来自EC LN的HIV特异性CD8 + T细胞之间的独特转录特征，其典型特征是抑制性受体和溶细胞分子的下调以及多种细胞因子的上调，预测的分泌因子，以及蛋白质翻译机器的组件。总的来说，这些结果提供了一个机制框架，可以加快新型抗病毒因子的鉴定，强调非溶细胞功能的局部部署作为抗 HIV 免疫功效的决定因素的潜在作用。