Heart failure & cardiomyopathies
Single-Cell Multi-Omics Identifies Specialized Cytotoxic and Migratory CD8 + Effector T Cells in Acute Myocarditis
Authors' conclusion
Our study provides a comprehensive immune landscape for understanding the pathogenesis of AM, especially in FM, highlighting clonal CD57+CD8+ effector T cells with high cytotoxicity and migration potential, along with their upstream inflammatory signals, as potential therapeutic targets for mitigating immune-related cardiac damage in AM management, especially in FM.
Study context
- Population
- Patients diagnosed with acute myocarditis, December 2022–November 2023; coxsackievirus B3-induced fulminant myocarditis (FM) mice
- Participants
- 40 patients
- Comparison
- Fulminant vs mild acute myocarditis
- Fulminantn = 16
- Mildn = 24reference
- Outcome
- Pathogenic immune subsets and molecular alterations in AM
Methodological detailssingle-cell multi-omics, coxsackievirus B3-induced FM mouse model, scRNA-seq, single-cell TCR sequencing, cytometry by time of flight and Olink proteomics of PBMCs and plasma
- Single-cell multi-omics
- Coxsackievirus B3-induced FM mouse model
- scRNA-seq, single-cell TCR sequencing, cytometry by time of flight and Olink proteomics of PBMCs and plasma
Main finding
As reported in the abstract
- CD57+CD8+ effector T cells with high cytotoxicity and migration potential substantially enriched, with large clonal expansion, in acute myocarditis (AM)
- Natural killer-like receptor genes upregulated in CD57+CD8+ effector T cells in FM vs mild, associated with enhanced cytotoxicity and migration potential
- In vitro, circulating CD57+CD8+ effector T cells with high cytotoxic degranulation and migration potential induced cardiomyocyte apoptosis
- Elevated circulating IL-18 in AM induced functional differentiation of CD57+CD8+ effector T cells
- Increased proinflammatory CXCL8+CD14+ monocytes potentially contributed to increasing IL-18 and crosstalk with CD57+CD8+ effector T cells
- In FM mice, analogous expansions of CD57+CD8+ effector T cells and CXCL2+LY6C+ monocytes in blood and hearts, with elevated plasma IL-18
- Disrupting proinflammatory monocytes, IL-18 signalling and CCR5-mediated cardiac recruitment significantly alleviated FM in mice
Original publication
Single-Cell Multi-Omics Identifies Specialized Cytotoxic and Migratory CD8 + Effector T Cells in Acute Myocarditis. Circulation. Published 5 August 2025. doi:10.
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