OBJECTIVE: Coronary heart disease (CHD) is associated with high morbidity and mortality worldwide. CD4?CD25?FOXP3? regulatory T cells (Tregs) play a role in the modulation of vascular inflammation. The negatively costimulatory molecule programmed cell death ligand 1 (PD-L1) exerts a prominent effect on the adjustment of immune responses. We investigated the relationship between the expression of PD-L1 on peripheral blood Tregs and the severity of CHD. METHODS AND RESULTS: Human peripheral blood was collected from 59 patients with CHD and 11 healthy volunteers. The expression of PD-L1 on peripheral blood Tregs was detected by flow cytometry, and the production of interleukin 2 (IL-2), IL-4, IL-10, and transforming growth factor β1 in plasma was determined using enzyme-linked immunosorbent assay. The subgroup of patients with acute coronary syndrome (ACS), which includes unstable angina pectoris, non-ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction, showed a significant reduction of FOXP3 and PD-L1 expression on Tregs compared with the subgroup of patients with chronic coronary artery disease, comprising stable angina pectoris, silent myocardial ischemia, and ischemic heart failure, and the control group. Moreover, the ACS group showed significantly increased production of IL-2, and decreased production of IL-4, IL-10, and transforming growth factor β1, compared with the coronary artery disease and control groups. CONCLUSION: Expression of the coinhibitory molecule PD-L1 on peripheral blood Tregs is correlated negatively with the severity of CHD and could serve as a novel indicator of ACS.