Regulatory/Effector T-Cell Ratio Is Reduced in Coronary Artery Disease

BACKGROUND: The protective function of regulatory T cells (Treg) has been identified in experimental atherosclerosis, but the contribution of Treg to the pathogenesis of human coronary artery disease (CAD) remains poorly understood. We investigated Treg and regulatory T-cell/effector T-cell (Treg/Teff) ratio in peripheral blood samples from CAD patients using a new strategy for precise identification of Treg. METHODS AND RESULTS: Peripheral blood samples were collected from 73 stable CAD patients (55 middle-aged CAD patients and 18 old CAD patients) and 64 controls (47 middle-aged controls and 17 young controls). CD3(+)CD4(+)FoxP3(+)T cells were divided into 3 fractions: CD45RA(+)FoxP3(low)resting Treg(Fr1), CD45RA(-)FoxP3(high)activated Treg(Fr2), and CD45RA(-)FoxP3(low)non-Treg(Fr3). CAD patients had lower percentages of Fr1 and Fr2 and higher percentages of Fr3 and CD45RA(-)Foxp3(-)Teff(Fr4+5) within the CD3(+)CD4(+)T-cell population compared to age-matched controls. Treg/Teff ratio (Fr1+2/Fr3+4+5) in CAD patients was also markedly lower than in controls (middle-aged control, 0.17±0.09 vs. middle-aged CAD, 0.10±0.05; P<0.001). The percentage of CD4(+)CD28(null)T cells within the CD4(+)T-cell population was negatively correlated with Treg/Teff ratio, excluding CD4(+)CD28(null)T cells <0.3% (r=-0.27, P<0.05). High-sensitivity C-reactive protein was also negatively correlated with Treg/Teff ratio (r=-0.22, P<0.05). CONCLUSIONS: CAD patients had reduced Treg and Treg/Teff ratio compared to healthy controls. The present findings may be helpful when developing immunotherapy for the prevention of CAD.