Characteristics and functions of an atypical inflammation-associated GZMK+GZMB+CD8+ T subset in people living with HIV-1

作者：Liang Zhao, Hui‐Fang Wang, Yu Zhang, Yanze Shi, Chun‐Bao Zhou, Minrui Yu, Yanhu Wang, Liping Zhang, Xu Zheng, Ziying Zhang, Lingyu Gao, Jiyuan Zhang, Baopeng Yang, Huihuang Huang, Fusheng Wang · 发表于：Molecular Immunology · 年份：2024 · DOI：10.1016/j.molimm.2024.07.003 · 被引用次数：8 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Immunodeficiency and Autoimmune Disorders

HIV-1 chronically infects host CD4+ T lymphocytes and further affects a variety of immune cells, including CD8+ T cells. In our previous study, by analyzing unbiased high-dimensional single-cell RNA-seq data (scRNA-seq), we found that the frequency of GZMK+CD8+ T cells expressing granzyme K (GZMK) was increased in people living with HIV-1 (PLWHs). However, the phenotypic and functional characteristics of these cells in chronic HIV-1 infection and their correlation with disease are not well understood. In this study, we conducted a comprehensive analysis of scRNA-seq and matched T-cell receptor repertoire (TCR) sequencing data to delve into the characterizations of GZMK+CD8+ T cells, which was further validated by flow cytometry. We observed heterogeneity within the GZMK+CD8+ T cells, which could be further subdivided into a GZMK+GZMB- subset and a GZMK+GZMB+ subset, with the latter being significantly enriched in PLWHs. The GZMK+GZMB+ cells are a unique subset within CD8+ T cells, characterized by high proliferation, activation, inflammatory response, clone transition, etc., and are one of the differentiation endpoints by pseudotemporal analysis of CD8+αβ T cells. Despite being predominantly composed of effector memory T cells (Tem), similar to the GZMK+GZMB- subset, the GZMK+GZMB+ subset exhibits differentiation at a later stage than the GZMK+GZMB- subset. We also observed that the frequency/count of GZMK+GZMB+CD8+ T cells was negatively correlated with CD4/CD8 ratio, and po...