Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Curr Opin Lipidol. 2018 Oct;29(5):411-416. doi: 10.1097/MOL.0000000000000541.
Atherosclerosis and the clinical consequence of cardiovascular disease remain the leading cause of death worldwide. Both an increase in cholesterol levels, as well as immune responses drive the pathogenesis of this disease. Although much is known about the role of many immune cell subsets in atherogenesis, research into the role of CD8 T cells is limited.
Both atheroprotective and atherogenic functions of CD8 T cells have been reported. On the one hand, the inflammatory cytokines produced by CD8 T cells exacerbate inflammatory responses, and the cytotoxic activity of these cells toward lesion-stabilizing cells such as endothelial cells drives the progression and instability of atherosclerotic lesions. On the other hand, cytotoxic activity toward antigen presenting cells and the presence of regulatory CD8 T-cell subsets dampen immunity and can limit atherosclerosis.
Here we review the different roles of CD8 T cells in atherosclerosis and discuss possible treatment strategies targeting these cells to reduce atherosclerotic lesion burden.
动脉粥样硬化和心血管疾病的临床后果仍然是全球死亡的主要原因。胆固醇水平的升高和免疫反应都驱动着这种疾病的发病机制。尽管人们对许多免疫细胞亚群在动脉粥样硬化形成中的作用有了很多了解,但对 CD8 T 细胞作用的研究是有限的。
已报道 CD8 T 细胞具有抗动脉粥样硬化和促动脉粥样硬化作用。一方面,CD8 T 细胞产生的炎症细胞因子加剧了炎症反应,而这些细胞对稳定病变的细胞(如内皮细胞)的细胞毒性活性则推动了动脉粥样硬化病变的进展和不稳定。另一方面,针对抗原呈递细胞的细胞毒性活性和调节性 CD8 T 细胞亚群的存在抑制了免疫反应,并可能限制动脉粥样硬化的发生。
本文综述了 CD8 T 细胞在动脉粥样硬化中的不同作用,并讨论了针对这些细胞的可能治疗策略,以减少动脉粥样硬化病变负担。