ACCELERATED CD8+ T CELL MATURATION IN INFANTS WITH PERINATAL HIV INFECTION

In perinatal HIV infection, early ART initiation is recommended but questions remain regarding infant immune responses to HIV and impact of HIV on immune development. Using single cell transcriptional and phenotypic analysis we evaluated the T cell compartment at pre-ART initiation of infants with perinatally acquired HIV from Maputo, Mozambique (TARA cohort). CD8+ T cell maturation subsets exhibited altered distribution in HIV exposed infected (HEI) infants relative to control infants (HIV exposed uninfected) with reduced naïve, increased effectors, higher frequencies of activated T cells, and lower frequencies of cells with markers of self-renewal. Additionally, a cluster of CD8+ T cells identified in HEI displayed gene profiles consistent with cytotoxic T lymphocytes (CTL) and showed evidence for hyper expansion. Longitudinal phenotypic analysis revealed accelerated maturation of CD8+ T cells was maintained in HEI despite viral control. The results point to a HIV directed immune response that is likely to influence reservoir establishment. Investigate gene expression profiles and T cell and B cell clonality in PBMC from 1 month old infants that aquired HIV perinatally.

围产期HIV感染领域目前推荐早期启动抗逆转录病毒治疗（ART），但仍存在诸多未解决的疑问，例如婴儿针对HIV的免疫应答情况，以及HIV对婴儿免疫发育的影响。本研究借助单细胞转录组与表型分析技术，对莫桑比克马普托地区围产期获得HIV感染婴儿在抗逆转录病毒治疗启动前的T细胞库进行了评估（该队列命名为TARA队列）。与对照组婴儿（HIV暴露未感染）相比，HIV暴露感染（HEI）婴儿的CD8+ T细胞成熟亚群分布发生改变：初始T细胞比例降低、效应T细胞比例升高，活化T细胞的占比更高，而表达自我更新标志物的细胞占比更低。此外，在HEI婴儿中鉴定出的一类CD8+ T细胞簇，其基因表达特征与细胞毒性T淋巴细胞（CTL）一致，且呈现出过度扩增的特征。纵向表型分析结果显示，即便实现病毒学控制，HEI婴儿体内的CD8+ T细胞成熟加速现象仍持续存在。上述研究结果表明，机体针对HIV的免疫应答或会对病毒储存库的建立产生影响。本研究将对1月龄围产期获得HIV感染婴儿的外周血单个核细胞（PBMC）的基因表达谱，以及T细胞与B细胞的克隆性展开分析。