Atherosclerotic cardiovascular disease (ASCVD) is a chronic inflammatory disease of the arterial walls and is characterized by the accumulation of lipoproteins that are insufficiently cleared by phagocytes. Following the initiation of atherosclerosis, the pathological progression is accelerated by engagement of the adaptive immune system. Atherosclerosis triggers the breakdown of tolerance to self-components. This loss of tolerance is reflected in defective expression of immune checkpoint molecules, dysfunctional antigen presentation, and aberrations in T cell populations — most notably in regulatory T (T_reg) cells — and in the production of autoantibodies. The breakdown of tolerance to self-proteins that is observed in ASCVD may be linked to the conversion of T_reg cells to ‘exT_reg’ cells because many T_reg cells in ASCVD express T cell receptors that are specific for self-epitopes. Alternatively, or in addition, breakdown of tolerance may trigger the activation of naive T cells, resulting in the clonal expansion of T cell populations with pro-inflammatory and cytotoxic effector phenotypes. In this Perspective, we review the evidence that atherosclerosis is associated with a breakdown of tolerance to self-antigens, discuss possible immunological mechanisms and identify knowledge gaps to map out future research. Rational approaches aimed at re-establishing immune tolerance may become game changers in treating ASCVD and in preventing its downstream sequelae, which include heart attacks and strokes.

动脉粥样硬化性心血管疾病（ASCVD）是一种动脉壁慢性炎症性疾病，其特征是吞噬细胞不能充分清除脂蛋白的积累。动脉粥样硬化开始后，适应性免疫系统的参与会加速病理进展。动脉粥样硬化会引发对自身成分耐受性的破坏。这种耐受性的丧失反映在免疫检查点分子的表达缺陷、抗原呈递功能失调、T 细胞群异常（最明显的是调节性 T (T _reg ) 细胞）以及自身抗体的产生中。_{ASCVD 中观察到的对自身蛋白耐受性的破坏可能与 T reg}细胞向“exT _reg ”细胞的转化有关，因为 ASCVD 中许多 T _reg细胞表达对自身表位具有特异性的 T 细胞受体。或者或此外，耐受性的破坏可能触发初始T细胞的激活，导致具有促炎和细胞毒性效应表型的T细胞群的克隆扩增。在本视角中，我们回顾了动脉粥样硬化与自身抗原耐受性破坏相关的证据，讨论了可能的免疫机制并确定了知识差距以规划未来的研究。旨在重建免疫耐受的合理方法可能会成为治疗 ASCVD 和预防其下游后遗症（包括心脏病和中风）的游戏规则改变者。