Expression of circulatory dendritic cells and regulatory T-cells in patients with different subsets of coronary artery disease.

BACKGROUND

Dendritic cells (DCs), regulators of innate and adaptive immunity, may play an important role in atherosclerosis. DC invasion was found in early atherosclerotic lesions. We aimed to characterize circulating DC gene expression in patients with different subsets of coronary artery disease (CAD).

METHODS

Peripheral blood mononuclear cells were quantified using real-time polymerase chain reaction and fluorescence activated cell sorting in patients with acute coronary syndrome (ST-elevation myocardial infarction [STEMI], n = 35; non-ST-elevation myocardial infarction [NSTEMI], n = 30) and stable CAD (6 months after stent implantation without progression, n = 15) compared with control subjects (n = 15). DCs and T-cells (TCs) were characterized using specific primers for CD1a (immature), CD86 (mature), CD123 (plasmacytoid), BDCA1 (myeloid), CD178 (activated TCs), and FOXP3 (regulatory TCs). To evaluate whether serum of patients with STEMI induces DC differentiation, incubation of patient serum was performed.

RESULTS

CD86 was upregulated and CD1a downregulated in all patients with CAD (P < 0.05). Patients with STEMI and NSTEMI showed a downregulation of CD1a compared with patients with stable CAD (P ≤ 0.01). In contrast, stable patients with CAD had elevated CD178 levels compared with patients with STEMI and NSTEMI (P ≤ 0.04). In patients with STEMI, FOXP3 was downregulated compared with control subjects (P < 0.0001). Incubation of STEMI serum induced an upregulation of CD1a and CD86 in a human DC cell line. Coincubation with a blocking antibody for heat shock protein 60 inhibited this upregulation.

CONCLUSIONS

DCs are differentially regulated in patients with different subsets of CAD. Mature DCs are upregulated and immature DCs are downregulated in patients with CAD. Patients with STEMI show a significant downregulation of regulatory TCs. Circulating shock protein 60 induces DC differentiation in patients with STEMI.