Subsets of tissue CD4 T cells display different susceptibilities to HIV infection and death: Analysis by CyTOF and single cell RNA-seq

CD4 T lymphocytes belong to diverse cellular subsets whose sensitivity or resistance to HIV-associated killing remains to be defined. Working with lymphoid cells from human tonsils, we characterized the HIV-associated depletion of various CD4 T cell subsets using mass cytometry and single-cell RNA-seq. CD4 T cell subsets preferentially killed by HIV are phenotypically distinct from those resistant to HIV-associated cell death, in a manner not fully accounted for by their susceptibility to productive infection. Preferentially-killed subsets express CXCR5 and CXCR4 while preferentially-infected subsets exhibit an activated and exhausted effector memory cell phenotype. Single-cell RNA-seq analysis reveals that the subsets of preferentially-killed cells express genes favoring abortive infection and pyroptosis. These studies emphasize a complex interplay between HIV and distinct tissue-based CD4 T cell subsets, and the important contribution of abortive infection and inflammatory programmed ..., mass cytometry; single-cell RNA-seq mass cytometry data has been pre-gated on live singlets and normalized by CD8 cell number single-cell RNA-seq data are raw data,CD4 T淋巴细胞（CD4 T Lymphocyte）属于异质性细胞亚群，其对HIV介导的杀伤作用的敏感性或抗性仍有待明确。本研究以人类扁桃体的淋巴样细胞为研究对象，采用质谱流式细胞术（Mass Cytometry）与单细胞RNA测序（Single-Cell RNA Sequencing）对多种CD4 T细胞亚群的HIV相关耗竭特征进行了表征。被HIV优先杀伤的CD4 T细胞亚群，其表型与对HIV介导的细胞死亡具有抗性的亚群截然不同，且这种差异无法完全用其对产毒性感染的易感性来解释。优先被杀伤的亚群表达CXCR5与CXCR4，而优先被感染的亚群则呈现活化且耗竭的效应记忆细胞表型。单细胞RNA测序分析显示，优先被杀伤的细胞亚群表达有利于顿挫感染（Abortive Infection）与焦亡（Pyroptosis）的基因。本研究强调了HIV与不同组织来源CD4 T细胞亚群之间存在复杂的相互作用，以及顿挫感染与炎症性程序性……的重要贡献。质谱流式细胞术；单细胞RNA测序 质谱流式细胞术数据已对活单细胞群进行预门控，并以CD8细胞计数进行归一化处理 单细胞RNA测序数据为原始数据