Andoh Yasuhiro, Fujii Satoshi, Iwabuchi Kazuya, Yokota Takashi, Inoue Naoki, Nakai Yukihito, Mishima Tetsuya, Yamashita Takehiro, Nakagawa Toshiaki, Kitabatake Akira, Onoe Kazunori, Tsutsui Hiroyuki
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Coron Artery Dis. 2006 Sep;17(6):523-8. doi: 10.1097/00019501-200609000-00005.
Atherosclerosis is an inflammatory disease. Natural killer T cells are a unique lymphocyte subset that can recognize lipid antigens presented by CD1d and secrete copious amounts of pro-atherogenic cytokines such as interferon-gamma. We have previously shown that natural killer T cells accelerate atherosclerosis in mice and macrophages incubated with oxidized low-density lipoproteins induce natural killer T cells to produce interferon-gamma. Thus, whether the prevalence of natural killer T cells in peripheral blood is altered in patients with angina pectoris and its correlation with coronary risk factors was determined.
Cell profiling was performed using flow cytometry in patients with stable angina, unstable angina (Braunwald IIIB), and healthy controls. Natural killer T cells in peripheral blood were identified by the expression of natural killer T specific invariant T cell receptor alpha-chain (Valpha24) and T cell receptor beta-chain (Vbeta11).
Prevalence of natural killer T (Valpha24-Vbeta11 double positive) cells was significantly decreased in patients with unstable angina and stable angina compared with that in controls. No significant differences were observed in the prevalence between unstable and stable angina. Reduction of natural killer T cells was independently associated with the presence of angina.
Lower prevalence of circulating natural killer T cells is related to the presence of coronary artery disease. As T cell receptor down-regulation or apoptosis after natural killer T cell activation and subsequent interferon-gamma release may contribute to atherogenesis, natural killer T cells can become a novel therapeutic target for the prevention and treatment of atherosclerotic vascular diseases.
动脉粥样硬化是一种炎症性疾病。自然杀伤T细胞是一种独特的淋巴细胞亚群，能够识别由CD1d呈递的脂质抗原并分泌大量促动脉粥样硬化细胞因子，如γ干扰素。我们之前已经表明，自然杀伤T细胞可加速小鼠动脉粥样硬化的发展，并且与氧化型低密度脂蛋白一起孵育的巨噬细胞可诱导自然杀伤T细胞产生γ干扰素。因此，我们确定了心绞痛患者外周血中自然杀伤T细胞的比例是否发生改变及其与冠状动脉危险因素的相关性。
使用流式细胞术对稳定型心绞痛患者、不稳定型心绞痛（Braunwald IIIB级）患者和健康对照者进行细胞分析。通过自然杀伤T细胞特异性恒定T细胞受体α链（Vα24）和T细胞受体β链（Vβ11）的表达来鉴定外周血中的自然杀伤T细胞。
与对照组相比，不稳定型心绞痛患者和稳定型心绞痛患者中自然杀伤T（Vα24-Vβ11双阳性）细胞的比例显著降低。不稳定型心绞痛和稳定型心绞痛患者之间的比例未观察到显著差异。自然杀伤T细胞的减少与心绞痛的存在独立相关。
循环中自然杀伤T细胞比例较低与冠状动脉疾病的存在有关。由于自然杀伤T细胞激活后T细胞受体下调或凋亡以及随后γ干扰素的释放可能促进动脉粥样硬化的发生，自然杀伤T细胞可成为预防和治疗动脉粥样硬化性血管疾病的新治疗靶点。
