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

Abstract

Background:The protective function of regulatory T cells (T_reg) has been identified in experimental atherosclerosis, but the contribution of T_regto the pathogenesis of human coronary artery disease (CAD) remains poorly understood. We investigated T_regand regulatory T-cell/effector T-cell (T_reg/T_eff) ratio in peripheral blood samples from CAD patients using a new strategy for precise identification of T_reg.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^lowresting T_reg(Fr1), CD45RA^–FoxP3^highactivated T_reg(Fr2), and CD45RA^–FoxP3^lownon-T_reg(Fr3). CAD patients had lower percentages of Fr1 and Fr2 and higher percentages of Fr3 and CD45RA^–Foxp3^–T_eff(Fr4+5) within the CD3⁺CD4⁺T-cell population compared to age-matched controls. T_reg/T_effratio (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^nullT cells within the CD4⁺T-cell population was negatively correlated with T_reg/T_effratio, excluding CD4⁺CD28^nullT cells <0.3% (r=–0.27, P<0.05). High-sensitivity C-reactive protein was also negatively correlated with T_reg/T_effratio (r=–0.22, P<0.05).Conclusions:CAD patients had reduced T_regand T_reg/T_effratio compared to healthy controls. The present findings may be helpful when developing immunotherapy for the prevention of CAD. (Circ J 2014; 78: 2935–2941)