Antigen-presenting cells drive early CD8+ T-cell recruitment in human myocardial infarction, while endothelial progenitor cell capacity inversely correlates with coronary lesion burden.
Spatial transcriptomics and functional profiling reveal that APC-driven CD8+ T-cell recruitment and endothelial progenitor cell dysfunction contribute to impaired vascular repair following human myocardial infarction.
Absolute Event Rate: 0% vs 0%
Background: In an earlier murine model of myocardial infarction (MI), we showed that CD8 cells and myeloid dendritic cells (mDCs) infiltrate the infarcted myocardium within the first week. However, in humans, the spatial interplay between CD8+ T cells and dendritic cells in the spatial context of human myocardial infarction remains underexplored. Objective: In the present study, we applied spatial transcriptomics and functional assays to characterize immune–stromal dynamics in infarcted myocardium and peripheral blood. Methods & Results: Spatial transcriptomics analysis of infarcted human myocardium at days 2 and 6 post-MI, combined with peripheral blood flow cytometry and EPC colony-forming assays, was performed. Cell composition, pathway enrichment, and cell-to-cell communication analyses were conducted to map immune–stromal cells’ dynamics across time points. Spatial mapping identified dynamic shifts in immune, fibroblast, and endothelial populations, with fibroblasts and endothelial cells remaining abundant throughout. CD8+ T cells accumulated in ischemic regions while their circulating levels declined. Gene Ontology and pathway analyses of CD8A+ transcripts revealed enrichment of proinflammatory and NF-κB survival programs. ITGAX/CD33/THBD+ APCs progressively increased within infarct zones, activating antigen-presentation and leukocyte chemotaxis pathways. Early (day 2) APC–endothelial crosstalk showed the strongest predicted recruitment signals for CD8+ T cells, which diminished by day 6. Finally, EPC colony-forming capacity showed a tendency for reduction in MI patients and inversely correlated with coronary lesion burden, indicating impaired vascular repair potential. Conclusions: This integrative spatial and functional study demonstrates that APC-driven CD8+ recruitment and EPC dysfunction are key features of human MI. Immune–endothelial niches facilitate early cytotoxic T-cell infiltration, while progenitor depletion limits vascular regeneration. These findings provide mechanistic insight into immune–vascular imbalance during infarct healing and highlight potential therapeutic targets to modulate inflammation and restore vascular repair.
Salybekov et al. (Thu,) reported a other. Antigen-presenting cells drive early CD8+ T-cell recruitment in human myocardial infarction, while endothelial progenitor cell capacity inversely correlates with coronary lesion burden.
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