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