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Chronic heart failure associates with enhanced activation and clonal expansion of T cells with predicted autoreactive capacity

Merten, M.; Rasper, T.; Holz, K.; Cremer, S.; Schuhmacher, B.; Tombor, L.; John, D.; Ullrich, E.; Macinkovic, I.; Leistner, D.; Hoffmann, J.; Speer, T.; Bonig, H.; Knosalla, C.; Potapov, E.; Sarapki, T.; Mustafic, E.; Berkowitsch, A.; Zeiher, A. M.; Dimmeler, S.; Abplanalp, W. T.

2025-04-16 cardiovascular medicine
10.1101/2025.04.14.25325772 medRxiv
Show abstract

Chronic heart failure (HF) is characterized by adverse remodeling and persistent inflammation, contributing to impaired heart function and poor prognosis. While the acute immune response post-myocardial infarction (MI) is well-studied, its role in chronic HF remains unclear. Phenotyping of peripheral blood T cells by flow cytometry and single-cell RNA sequencing revealed T central memory cells (TCM) decline, while CD4+ Th17 and CD8+ T effector memory cells increase in HF patients compared to healthy age-matched controls. Furthermore, this decline in TCM cells and increase in homing marker CCR5 on T cell subsets associates with poor prognosis in HF. T cell receptor sequencing revealed clonal expansion in circulating and cardiac T cells, while epitope prediction modeling suggested autoreactivity of T cells in HF. Spatial and scRNA-seq data confirm inflammatory T cell infiltration in the human and murine heart post-MI. In summary, HF shows potential autoreactivity, with an increased homing capacity and declining TCM cells associated with poor prognosis.

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