Virus-Associated CD8+ T-Cells Are Not Activated Through Antigen-Mediated Interaction Inside Atherosclerotic Lesions
INTRODUCTION: Viral infections have been associated with the progression of atherosclerosis and CD8+ T-cells directed against common viruses, such as influenza, Epstein-Barr virus, and cytomegalovirus, have been detected inside human atherosclerotic lesions. These virus-specific CD8+ T-cells have been hypothesized to contribute to the development of atherosclerosis; however, whether they affect disease progression directly remains unclear. In this study, we aimed to characterize the activation status of virus-specific CD8+ T-cells in the atherosclerotic lesion.
METHODS: The presence, clonality, tissue enrichment, and phenotype of virus-associated CD8+ T-cells in atherosclerotic lesions were assessed by exploiting bulk T-cell receptor-β sequencing and single-cell T-cell receptor (α and β) sequencing datasets on human endarterectomy samples and patient-matched blood samples. To investigate if virus-specific CD8+ T-cells can be activated through T-cell receptor stimulation in the atherosclerotic lesion, the immunopeptidome of human plaques was determined.
RESULTS: Virus-associated CD8+ T-cells accumulated more in the atherosclerotic lesion (mean=2.0%), compared with patient-matched blood samples (mean=1.4%; P=0.05), and were more clonally expanded and tissue enriched in the atherosclerotic lesion in comparison with nonassociated CD8+ T-cells from the lesion. Single-cell T-cell receptor sequencing and flow cytometry revealed that these virus-associated CD8+ T-cells were phenotypically highly similar to other CD8+ T-cells in the lesion and that both exhibited a more activated phenotype compared with circulating T-cells. Interestingly, virus-associated CD8+ T-cells are unlikely to be activated through antigen-specific interactions in the atherosclerotic lesion, as no virus-derived peptides were detected on HLA-I in the lesion.
CONCLUSIONS: This study suggests that virus-specific CD8+ T-cells are tissue enriched in atherosclerotic lesions; however, their potential contribution to inflammation may involve antigen-independent mechanisms.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Arteriosclerosis, thrombosis, and vascular biology - (2024) vom: 21. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
de Jong, Maaike J M [VerfasserIn] |
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| Links: |
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| Themen: |
Antigen presentation |
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| Anmerkungen: |
Date Revised 21.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1161/ATVBAHA.123.320539 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 100 | 1 | |a de Jong, Maaike J M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Virus-Associated CD8+ T-Cells Are Not Activated Through Antigen-Mediated Interaction Inside Atherosclerotic Lesions |
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| 520 | |a INTRODUCTION: Viral infections have been associated with the progression of atherosclerosis and CD8+ T-cells directed against common viruses, such as influenza, Epstein-Barr virus, and cytomegalovirus, have been detected inside human atherosclerotic lesions. These virus-specific CD8+ T-cells have been hypothesized to contribute to the development of atherosclerosis; however, whether they affect disease progression directly remains unclear. In this study, we aimed to characterize the activation status of virus-specific CD8+ T-cells in the atherosclerotic lesion | ||
| 520 | |a METHODS: The presence, clonality, tissue enrichment, and phenotype of virus-associated CD8+ T-cells in atherosclerotic lesions were assessed by exploiting bulk T-cell receptor-β sequencing and single-cell T-cell receptor (α and β) sequencing datasets on human endarterectomy samples and patient-matched blood samples. To investigate if virus-specific CD8+ T-cells can be activated through T-cell receptor stimulation in the atherosclerotic lesion, the immunopeptidome of human plaques was determined | ||
| 520 | |a RESULTS: Virus-associated CD8+ T-cells accumulated more in the atherosclerotic lesion (mean=2.0%), compared with patient-matched blood samples (mean=1.4%; P=0.05), and were more clonally expanded and tissue enriched in the atherosclerotic lesion in comparison with nonassociated CD8+ T-cells from the lesion. Single-cell T-cell receptor sequencing and flow cytometry revealed that these virus-associated CD8+ T-cells were phenotypically highly similar to other CD8+ T-cells in the lesion and that both exhibited a more activated phenotype compared with circulating T-cells. Interestingly, virus-associated CD8+ T-cells are unlikely to be activated through antigen-specific interactions in the atherosclerotic lesion, as no virus-derived peptides were detected on HLA-I in the lesion | ||
| 520 | |a CONCLUSIONS: This study suggests that virus-specific CD8+ T-cells are tissue enriched in atherosclerotic lesions; however, their potential contribution to inflammation may involve antigen-independent mechanisms | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a antigen presentation | |
| 650 | 4 | |a atherosclerosis | |
| 650 | 4 | |a inflammation | |
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| 700 | 1 | |a Schaftenaar, Frank H |e verfasserin |4 aut | |
| 700 | 1 | |a Depuydt, Marie A C |e verfasserin |4 aut | |
| 700 | 1 | |a Lozano Vigario, Fernando |e verfasserin |4 aut | |
| 700 | 1 | |a Janssen, George M C |e verfasserin |4 aut | |
| 700 | 1 | |a Peeters, Judith A H M |e verfasserin |4 aut | |
| 700 | 1 | |a Goncalves, Lauren |e verfasserin |4 aut | |
| 700 | 1 | |a Wezel, Anouk |e verfasserin |4 aut | |
| 700 | 1 | |a Smeets, Harm J |e verfasserin |4 aut | |
| 700 | 1 | |a Kuiper, Johan |e verfasserin |4 aut | |
| 700 | 1 | |a Bot, Ilze |e verfasserin |4 aut | |
| 700 | 1 | |a van Veelen, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Slütter, Bram |e verfasserin |4 aut | |
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