Journal Article Case Reports Ppublish 4 citations
PubMed: 40522253 DOI: 10.1111/liv.70172
Analysis of Hyperexpanded T Cell Clones in SARS-CoV-2 Vaccine-Associated Liver Injury by Spatial Proteomics and Transcriptomics.
Liver Int 45(7):e70172
Authors: Sarp Uzun, Asmita Pant, Ewelina Bartoszek, Paul Gueguen, Stefan Frei, Hélène Heusler, Ilaria Arborelli, Carl Philipp Zinner, Neşe Karadağ Soylu, Benedetta Terziroli Beretta-Piccoli, Cumali Efe, Matthias S Matter
Affiliations
- Institute of Pathology, University Hospital of Basel, University of Basel, Basel, Switzerland.
- Microscopy Core Facility, Department of Biomedicine, University of Basel, Basel, Switzerland.
- Functional Genomics Center Zurich, ETH Zurich/University of Zurich, Zurich, Switzerland.
- Department of Pathology, University of Health Sciences, Adana City Education and Research Hospital, Adana, Turkey.
- Servizio di Gastroenterologia Ed Epatologia, Ente Ospedaliero Cantonale, Ospedale Civico, Lugano, Switzerland.
- Faculty of Medical Biosciences, Università della Svizzera Italiana, Lugano, Switzerland.
- MowatLabs, Faculty of Life Sciences & Medicine, King's College London, King's College Hospital, London, UK.
- Department of Gastroenterology, Harran University Hospital, Şanlıurfa, Turkey.
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.
MeSH
Cells, Hepatitis, Autoimmune, Sars-Cov-2, Vaccines, Covid-19 Vaccines, Liver, Vaccination, Proteomics, Severe Acute Respiratory Syndrome-Related Coronavirus, Tissues, Clone Cells, T-Lymphocytes, Spatial Transcriptomics