Killer cells in atherosclerosis
Killer cells in atherosclerosis
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DOI：
10.1016/j.ejphar.2017.05.009
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发表时间：
2017-12-05
影响因子：
5
通讯作者：
Bobik, Alex
中科院分区：
文献类型：
--
作者：
Kyaw, Tin;Tipping, Peter;Bobik, Alex
细胞毒性淋巴细胞（杀伤细胞）在宿主防御机制中发挥关键作用，保护免受感染和肿瘤监视。它们还可以在慢性炎症性疾病和自身免疫性疾病中发挥有害作用。组织细胞死亡和坏死是晚期动脉粥样硬化病变的显著特征，包括易受损/不稳定病变，其是大多数心脏病发作和中风的主要原因。杀伤细胞在人类和小鼠病变中的积累及其细胞毒性潜力的证据强烈表明，这些细胞有助于病变中的细胞死亡和坏死，导致易损斑块的发展和潜在的斑块破裂。杀伤细胞可以分为两组，适应性和先天性免疫细胞，这取决于它们是否需要抗原呈递来激活。活化的杀伤细胞检测受损或应激的细胞，并通过细胞毒性机制杀死，包括穿孔素、颗粒酶、TRAIL或FasL，在某些情况下还包括TNF-α。在这篇综述中，我们检查目前的知识在动脉粥样硬化中的杀伤细胞，包括CD 8 T细胞，CD 28-CD 4 T细胞，自然杀伤细胞和γ δ-T细胞，负责其激活的机制，其迁移到发展中的病变和效应功能。我们还讨论了通过预防/限制其在动脉粥样硬化病变内的细胞毒性作用来预防其有害血管效应的药理学策略，以及可能更好地靶向病变驻留杀伤细胞的潜在免疫调节疗法，以最大限度地减少免疫系统的任何损害，这可能导致对感染的易感性增加和肿瘤监测的减少。
Cytotoxic lymphocytes (killer cells) play a critical role in host defence mechanisms, protecting against infections and in tumour surveillance. They can also exert detrimental effects in chronic inflammatory disorders and in autoimmune diseases. Tissue cell death and necrosis are prominent features of advanced atherosclerotic lesions including vulnerable/unstable lesions which are largely responsible for most heart attacks and strokes. Evidence for accumulation of killer cells in both human and mouse lesions together with their cytotoxic potential strongly suggest that these cells contribute to cell death and necrosis in lesions leading to vulnerable plaque development and potentially plaque rupture. Killer cells can be divided into two groups, adaptive and innate immune cells depending on whether they require antigen presentation for activation. Activated killer cells detect damaged or stressed cells and kill by cytotoxic mechanisms that include perforin, granzymes, TRAIL or FasL and in some cases TNF-alpha. In this review, we examine current knowledge on killer cells in atherosclerosis, including CD8 T cells, CD28-CD4 T cells, natural killer cells and gamma delta-T cells, mechanisms responsible for their activation, their migration to developing lesions and effector functions. We also discuss pharmacological strategies to prevent their deleterious vascular effects by preventing/limiting their cytotoxic effects within atherosclerotic lesions as well as potential immunomodulatory therapies that might better target lesion-resident killer cells, to minimise any compromise of the immune system, which could result in increased susceptibility to infections and reductions in tumour surveillance.