tetano
Editor, Senior Moderator
Liver Int
. 2025 Jul;45(7):e70172.
doi: 10.1111/liv.70172. Analysis of Hyperexpanded T Cell Clones in SARS-CoV-2 Vaccine-Associated Liver Injury by Spatial Proteomics and Transcriptomics
Sarp Uzun[SUP] 1 [/SUP], Asmita Pant[SUP] 1 [/SUP], Ewelina Bartoszek[SUP] 2 [/SUP], Paul Gueguen[SUP] 3 [/SUP], Stefan Frei[SUP] 1 [/SUP], Hélène Heusler[SUP] 1 [/SUP], Ilaria Arborelli[SUP] 1 [/SUP], Carl Philipp Zinner[SUP] 1 [/SUP], Neşe Karadağ Soylu[SUP] 4 [/SUP], Benedetta Terziroli Beretta-Piccoli[SUP] 5 6 7 [/SUP], Cumali Efe[SUP] 8 [/SUP], Matthias S Matter[SUP] 1 [/SUP]
Affiliations
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.
Keywords: COVID‐19; SARS‐CoV‐2; autoimmune hepatitis; vaccination; vaccine‐induced liver injury.
. 2025 Jul;45(7):e70172.
doi: 10.1111/liv.70172. Analysis of Hyperexpanded T Cell Clones in SARS-CoV-2 Vaccine-Associated Liver Injury by Spatial Proteomics and Transcriptomics
Sarp Uzun[SUP] 1 [/SUP], Asmita Pant[SUP] 1 [/SUP], Ewelina Bartoszek[SUP] 2 [/SUP], Paul Gueguen[SUP] 3 [/SUP], Stefan Frei[SUP] 1 [/SUP], Hélène Heusler[SUP] 1 [/SUP], Ilaria Arborelli[SUP] 1 [/SUP], Carl Philipp Zinner[SUP] 1 [/SUP], Neşe Karadağ Soylu[SUP] 4 [/SUP], Benedetta Terziroli Beretta-Piccoli[SUP] 5 6 7 [/SUP], Cumali Efe[SUP] 8 [/SUP], Matthias S Matter[SUP] 1 [/SUP]
Affiliations
- PMID: 40522253
- DOI: 10.1111/liv.70172
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.
Keywords: COVID‐19; SARS‐CoV‐2; autoimmune hepatitis; vaccination; vaccine‐induced liver injury.