Table 5_Single-cell and spatial transcriptomics reveal transplant-associated T cells and myeloid cells in human liver transplantation.xlsx

BackgroundLiver transplantation is the only effective way for end-stage liver disease. Rejection remains the leading cause of graft failure. The dynamic changes of intrahepatic immune cells involved in rejection are not completely understood.
MethodsWe integrated single-cell RNA sequencing and spatial transcriptomics (ST) to analyze graft tissues from multiple stages of human liver transplantation. ST enabled high-resolution mapping of immune cell states and spatial distribution within liver grafts.
ResultsWe identified several transplantation-associated T cell (taT) subsets, including CD4+ effector-like T cells (Teff_like), CD8+ precursor exhausted T cells (Tpex), and CD8+ transitional effector-like T cells (tTeff_like). The CD4+ Teff_like subset highly expressed chemokines such as CCL3. The CD8+ tTeff_like subset represented an intermediate state transitioning from the CD8+ Tpex subset toward terminal exhaustion and was enriched in the immune activity pathway. Monocyte_PPARG, enriched in the rejection group, may be recruited by CD4+ Teff_like via the MIF-(CD74+CD44) pathway and subsequently promote CD8+ Tpex to tTeff_like differentiation through the ICAM1-LFA1 pathway. ST suggested that these immune subsets dominated the rejecting liver grafts.
ConclusionThese findings highlight the potential roles and spatial distribution of taT subsets in rejecting liver grafts, providing insights into local immune regulation and the development of targeted therapeutic strategies.

背景：肝移植是终末期肝病唯一有效的根治性治疗手段。排斥反应仍是移植器官失功的首要诱因，目前学界对于排斥反应相关的肝内免疫细胞动态变化机制尚未完全明晰。
方法：本研究整合单细胞RNA测序（single-cell RNA sequencing）与空间转录组学（spatial transcriptomics, ST）技术，对不同临床阶段的人类肝移植移植物组织开展分析。空间转录组学可实现肝移植物内免疫细胞状态与空间分布的高分辨率测绘。
结果：本研究鉴定出多种移植相关T细胞（transplantation-associated T cell, taT）亚群，包括CD4+效应样T细胞（CD4+ effector-like T cells, Teff_like）、CD8+前体耗竭T细胞（CD8+ precursor exhausted T cells, Tpex）以及CD8+过渡型效应样T细胞（CD8+ transitional effector-like T cells, tTeff_like）。其中CD4+ Teff_like亚群高表达CCL3等趋化因子；CD8+ tTeff_like亚群是从CD8+ Tpex亚群向终末耗竭状态转化的中间表型，且显著富集于免疫激活通路中。富集于排斥反应组的Monocyte_PPARG亚群，可能通过MIF-(CD74+CD44)通路被CD4+ Teff_like亚群招募，并随后通过ICAM1-LFA1通路促进CD8+ Tpex向tTeff_like亚群分化。空间转录组学分析显示，上述免疫亚群在发生排斥反应的肝移植物中占据免疫主导地位。
结论：本研究结果阐明了移植相关T细胞亚群在排斥反应肝移植物中的潜在作用与空间分布特征，为局部免疫调控机制研究及靶向治疗策略的开发提供了全新的理论依据与研究方向。