Abstract：
Human immunodeficiency virus (HIV) cure efforts are increasingly focused on harnessing CD8+ T cell functions, which requires a deeper understanding of CD8+ T cells promoting HIV control. Here we identifiy an antigen-responsive TOXhiTCF1+CD39+CD8+ T cell population with high expression of inhibitory receptors and low expression of canonical cytolytic molecules. Transcriptional analysis of simian immunodeficiency virus (SIV)-specific CD8+ T cells and proteomic analysis of purified CD8+ T cell subsets identified TOXhiTCF1+CD39+CD8+ T cells as intermediate effectors that retained stem-like features with a lineage relationship with terminal effector T cells. TOXhiTCF1+CD39+CD8+ T cells were found at higher frequency than TCF1-CD39+CD8+ T cells in follicular microenvironments and were preferentially located in proximity of SIV-RNA+ cells. Their frequency was associated with reduced plasma viremia and lower SIV reservoir size. Highly similar TOXhiTCF1+CD39+CD8+ T cells were detected in lymph nodes from antiretroviral therapy-naive and antiretroviral therapy-suppressed people living with HIV, suggesting this population of CD8+ T cells contributes to limiting SIV and HIV persistence.
摘要：
人类免疫缺陷病毒（HIV）治疗的努力越来越集中在利用CD8+T细胞的功能，这需要对CD8+T细胞促进HIV控制有更深入的了解。在这里，我们确定了具有高表达抑制性受体和低表达经典溶细胞分子的抗原响应性TOXhiTCF1CD39CD8T细胞群。猿猴免疫缺陷病毒（SIV）特异性CD8T细胞的转录分析和纯化的CD8T细胞亚群的蛋白质组学分析将TOXhiTCF1CD39CD8T细胞鉴定为中间效应子，保留了与末端效应T细胞具有谱系关系的茎样特征。在卵泡微环境中，TOXhiTCF1CD39CD8T细胞的频率高于TCF1-CD39CD8T细胞，并且优先位于SIV-RNA细胞附近。它们的频率与降低的血浆病毒血症和降低的SIV储层大小有关。在首次接受抗逆转录病毒治疗和抗逆转录病毒治疗抑制HIV感染者的淋巴结中检测到高度相似的TOXhiTCF1+CD39+CD8+T细胞，这表明CD8+T细胞群有助于限制SIV和HIV的持续存在。
