高分辨率表型分析早期急性排斥反应揭示了保守的同种免疫特征。

High-resolution phenotyping of early acute rejection reveals a conserved alloimmune signature.

机构信息

Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA, USA; Stanford Immunology, Stanford University School of Medicine, Stanford, CA, USA.

Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA, USA.

出版信息

Cell Rep. 2021 Mar 2;34(9):108806. doi: 10.1016/j.celrep.2021.108806.

DOI:10.1016/j.celrep.2021.108806

PMID:33657374

Abstract

Alloimmune responses in acute rejection are complex, involving multiple interacting cell types and pathways. Deep profiling of these cell types has been limited by technology that lacks the capacity to resolve this high dimensionality. Single-cell mass cytometry is used to characterize the alloimmune response in early acute rejection, measuring 37 parameters simultaneously, across multiple time points in two models: a murine cardiac and vascularized composite allotransplant (VCA). Semi-supervised hierarchical clustering is used to group related cell types defined by combinatorial expression of surface and intracellular proteins, along with markers of effector function and activation. This expression profile is mapped to visualize changes in antigen composition across cell types, revealing phenotypic signatures in alloimmune T cells, natural killer (NK) cells, and myeloid subsets that are conserved and that firmly distinguish rejecting from non-rejecting grafts. These data provide a comprehensive, high-dimensional profile of cellular rejection after allograft transplantation.

摘要

同种异体免疫反应在急性排斥中较为复杂，涉及多种相互作用的细胞类型和途径。由于技术的限制，缺乏解析这种高维度的能力，因此对这些细胞类型的深入分析受到了限制。单细胞质谱流式细胞术用于在早期急性排斥中描述同种异体免疫反应，在两个模型（小鼠心脏和血管化复合同种异体移植）中同时测量 37 个参数，横跨多个时间点。半监督分层聚类用于根据表面和细胞内蛋白的组合表达以及效应功能和激活的标志物来对相关细胞类型进行分组。该表达谱用于可视化细胞类型之间抗原组成的变化，揭示同种异体 T 细胞、自然杀伤 (NK) 细胞和髓样细胞亚群中的表型特征，这些特征是保守的，并且可以明确区分排斥和非排斥移植物。这些数据提供了同种异体移植后细胞排斥的全面、高维特征。