Gladstone Institute of Virology, San Francisco, CA, United States.
Department of Urology, University of California, San Francisco, San Francisco, CA, United States.
Front Immunol. 2022 Jun 16;13:883420. doi: 10.3389/fimmu.2022.883420. eCollection 2022.
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 cell death to the overall depletion of CD4 T cells that accompanies untreated HIV infection.
CD4 T 淋巴细胞属于多种细胞亚群，其对 HIV 相关杀伤的敏感性或抗性仍有待确定。我们使用来自人扁桃体的淋巴细胞进行研究，通过质谱流式细胞术和单细胞 RNA 测序来描述各种 CD4 T 细胞亚群与 HIV 相关的耗竭情况。以一种尚未完全阐明的方式，被 HIV 优先杀伤的 CD4 T 细胞亚群在表型上与那些对 HIV 相关细胞死亡有抗性的亚群不同，而不是由其对有效感染的敏感性决定的。优先杀伤的亚群表达 CXCR5 和 CXCR4，而优先感染的亚群表现出激活和耗竭的效应记忆细胞表型。单细胞 RNA 测序分析显示，优先杀伤细胞的亚群表达有利于流产感染和细胞焦亡的基因。这些研究强调了 HIV 与不同组织来源的 CD4 T 细胞亚群之间的复杂相互作用，以及流产感染和炎症程序性细胞死亡对未经治疗的 HIV 感染伴随的 CD4 T 细胞总体耗竭的重要贡献。
