Analysis of Hyperexpanded T Cell Clones in <scp>SARS</scp> ‐ <scp>CoV</scp> ‐2 Vaccine‐Associated Liver Injury by Spatial Proteomics and Transcriptomics
Sarp Uzun, Asmita Pant, Ewelina M. Bartoszek, Paul Gueguen, Stefan Frei, Hélène Heusler, Ilaria Arborelli, Carl Zinner, Neşe Karadağ Soylu, Benedetta Terziroli Beretta‐Piccoli, Cumali Efe, Matthias S. Matter
Abstract
BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.