BACKGROUND: Persistent inflammation is linked to poor outcomes in patients with a history of myocardial infarction. The inflammatory state has been associated with activation of neutrophils as well as with regulatory T-cell (T reg ) deficiency. The role of T regs in the regulation of neutrophil survival has been postulated recently. Here, we investigated neutrophil apoptosis along with the potential impact of T regs on neutrophil apoptosis in patients with postmyocardial infarction chronic coronary syndrome, compared with healthy controls. METHODS: Twenty patients and 19 controls were included. Neutrophil apoptosis was assessed after 5-hour culture with or without IL (interleukin)-10, TNF (tumor necrosis factor), or lipopolysaccharide. Neutrophil phenotype was evaluated through flow cytometry analysis of surface receptors (CD66b and CXCR4) and ex vivo release of cytokines and proteins. The ability of T regs to induce neutrophil apoptosis was examined in autologous neutrophil-T reg cocultures. RESULTS: Spontaneous neutrophil apoptosis was significantly delayed in patients compared with controls (10.3% versus 19.2%, P =0.025). Also, neutrophils from patients overexpressed CD66b and CXCR4 and were more prone to release proinflammatory mediators. Notably, T regs induced neutrophil apoptosis in healthy subjects, but not in patients, indicating a loss of T reg -mediated regulation in the latter. There was no evidence that IL-10 had any influence on neutrophil apoptosis. However, cell-to-cell contact was found essential for T reg -induced neutrophil apoptosis. CONCLUSIONS: Patients with postmyocardial infarction chronic coronary syndrome display delayed neutrophil apoptosis and a proinflammatory neutrophil phenotype that is resistant to T reg -mediated apoptosis. Neutrophil dysfunction may contribute to persistent inflammation in patients with postmyocardial infarction chronic coronary syndrome, and as such constitutes a novel therapeutic target.
Schneider et al. (Thu,) studied this question.