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Background

Persistent inflammation is linked to poor outcomes in patients with chronic coronary syndrome (CCS). The inflammatory state in atherosclerotic disease 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 CCS, compared to healthy controls.

Methods

Twenty patients with CCS and 19 healthy controls were included. Neutrophil apoptosis was assessed after 5h culture with or without interleukin(IL-)10, TNF or LPS. Neutrophil phenotype was evaluated through flow cytometry analysis of surface receptors (CD66b and CXCR4) and ex vivo release of cytokines and granule proteins. The ability of T _regs to induce neutrophil apoptosis was examined in autologous neutrophil-T _reg co-cultures.

Results

Spontaneous neutrophil apoptosis was significantly delayed in patients compared to controls (10.3% vs. 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 CCS display delayed neutrophil apoptosis and a pro-inflammatory neutrophil phenotype that is resistant to T _reg -mediated apoptosis. Neutrophil dysfunction may contribute to persistent inflammation in patients with CCS, and as such constitute a novel therapeutic target.