Uzun Sarp, Pant Asmita, Bartoszek Ewelina, Gueguen Paul, Frei Stefan, Heusler Hélène, Arborelli Ilaria, Zinner Carl Philipp, Soylu Neşe Karadağ, Terziroli Beretta-Piccoli Benedetta, Efe Cumali, Matter Matthias S
Institute of Pathology, University Hospital of Basel, University of Basel, Basel, Switzerland.
Microscopy Core Facility, Department of Biomedicine, University of Basel, Basel, Switzerland.
Liver Int. 2025 Jul;45(7):e70172. doi: 10.1111/liv.70172.
SARS-CoV-2 vaccine-associated liver injury (SVALI) is a rare event and its pathophysiology remains unclear. Previous studies have found an oligoclonal CD8+ T cell infiltrate and SARS-CoV-2 spike antigen-specific T cells in the liver of patients with SVALI. Therefore, we aimed to characterise the immune infiltrate in a liver explant from a patient with severe SVALI.
T cell receptor sequencing, a novel combined multiplex immunofluorescence (mIF)-RNA in situ hybridisation (RISH) approach, and single cell spatial transcriptomics with the Xenium in situ platform were used to identify, track and characterise specific T cell clones in this liver sample.
T cell repertoire analysis revealed hyperexpanded clones with CDR3 sequences similar to previously identified SARS-CoV-2 spike antigen-specific T cells. The hyperexpanded clones were localised throughout the whole liver, but the concentration was higher at the portal interface. Many hyperexpanded T cells expressed cytotoxic granzymes A, B and K, but also tissue-resident markers such as CXCR6, CD69 and KLRB1.
Spatial proteomics and spatial transcriptomics techniques allowed the localisation and characterisation of hyperexpanded CD8+ T cell clones at single cell level. They exhibited cytotoxic and tissue-resident memory properties, suggesting their involvement in the pathogenesis of SVALI.
新型冠状病毒2型疫苗相关肝损伤（SVALI）是一种罕见事件，其病理生理学仍不清楚。既往研究在SVALI患者肝脏中发现寡克隆CD8+T细胞浸润及新型冠状病毒2型刺突抗原特异性T细胞。因此，我们旨在对一名重症SVALI患者肝脏外植体中的免疫浸润进行特征分析。
采用T细胞受体测序、一种新型的多重免疫荧光（mIF）-RNA原位杂交（RISH）联合方法以及使用Xenium原位平台的单细胞空间转录组学技术，对该肝脏样本中的特异性T细胞克隆进行识别、追踪和特征分析。
T细胞受体谱分析显示存在高度扩增的克隆，其互补决定区3（CDR3）序列与先前鉴定的新型冠状病毒2型刺突抗原特异性T细胞相似。高度扩增的克隆遍布整个肝脏，但在门静脉界面处浓度更高。许多高度扩增的T细胞表达细胞毒性颗粒酶A、B和K，同时也表达组织驻留标志物，如CXCR6、CD69和KLRB1。
空间蛋白质组学和空间转录组学技术能够在单细胞水平上对高度扩增的CD8+T细胞克隆进行定位和特征分析。它们表现出细胞毒性和组织驻留记忆特性，提示其参与了SVALI的发病机制。
