Neutrophils Exhibit Delayed Spontaneous Apoptosis and Resistance to Regulatory T-Cell-Induced Apoptosis in Patients...

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.

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 [cluster of differentiation] and CXCR4 [C-X-C chemokine receptor type 4]) 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.

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.

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.