A stage-based framework to interpret regulatory T cell biology after heart transplantation

Regulatory T cells play a pivotal role in immune responses following heart transplantation, influencing the entire post-transplant process. This article examines Treg dynamics in a stage-specific framework and their clinical implications. In the early phase (0–30 days), dominated by injury-related sterile inflammation, Treg recruitment affects local inflammation resolution and tissue repair, potentially altering risks of early immune injury and rejection. The intermediate phase (1–6 months) features high acute cellular rejection risk with ongoing immunosuppression adjustments; Treg quantity, phenotype, and suppressive function are closely associated with the regulation of anti-donor immune responses. In the late phase (>6 months), chronic low-grade inflammation and progressive vascular remodeling predominate, where Tregs suppress persistent immune attacks but may promote fibrosis via repair pathways, exhibiting bidirectional effects. This article highlights Treg detection limitations, including FOXP3 specificity, epigenetic stability, and blood-graft discrepancies. Future directions encompass multimarker monitoring, dynamic risk models, Treg cell therapy, and interventions like cytokine/microbiome modulation to achieve precise immunoregulation, reduce rejection, minimize complications, and improve long-term graft survival.