Key Points CD28null T cells show high reactivity of β2 integrin upon chemokine stimulation. ROS-mediated Ca2+ release is critical for β2 integrin activation in T cells. Spontaneous β2 integrin activity of CD28null T cells in ACS is ROS dependent. The number and activity of T cell subsets in the atherosclerotic plaques are critical for the prognosis of patients with acute coronary syndrome. β2 Integrin activation is pivotal for T cell recruitment and correlates with future cardiac events. Despite this knowledge, differential regulation of adhesiveness in T cell subsets has not been explored yet. In this study, we show that in human T cells, SDF-1α–mediated β2 integrin activation is driven by a, so far, not-described reactive oxidative species (ROS)–regulated calcium influx. Furthermore, we show that CD4+CD28null T cells represent a highly reactive subset showing 25-fold stronger β2 integrin activation upon SDF-1α stimulation compared with CD28+ T cells. Interestingly, ROS-dependent Ca release was much more prevalent in the pathogenetically pivotal CD28null subset compared with the CD28+ T cells, whereas the established mediators of the classical pathways for β2 integrin activation (PKC, PI3K, and PLC) were similarly activated in both T cell subsets. Thus, interference with the calcium flux attenuates spontaneous adhesion of CD28null T cells from acute coronary syndrome patients, and calcium ionophores abolished the observed differences in the adhesion properties between CD28+ and CD28null T cells. Likewise, the adhesion of these T cell subsets was indistinguishable in the presence of exogenous ROS/H2O2. Together, these data provide a molecular explanation of the role of ROS in pathogenesis of plaque destabilization.

中文翻译：

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反应性氧化物质-调节的 Ca2+ 释放调节 β2 整合素对急性冠状动脉综合征患者 CD4+ CD28null T 细胞的激活

关键点 CD28null T 细胞在趋化因子刺激下表现出 β2 整合素的高反应性。ROS 介导的 Ca2+ 释放对于 T 细胞中的 β2 整合素激活至关重要。ACS 中 CD28null T 细胞的自发 β2 整合素活性是 ROS 依赖性的。动脉粥样硬化斑块中T细胞亚群的数量和活性对急性冠脉综合征患者的预后至关重要。β2 整合素激活是 T 细胞募集的关键，并与未来的心脏事件相关。尽管有这些知识，但尚未探索 T 细胞亚群中粘附性的差异调节。在这项研究中，我们表明在人类 T 细胞中，SDF-1α 介导的 β2 整合素激活是由迄今为止尚未描述的活性氧化物质 (ROS) 调节的钙流入驱动的。此外，我们表明 CD4+CD28null T 细胞代表了一个高反应性子集，与 CD28+T 细胞相比，在 SDF-1α 刺激下显示出 25 倍强的 β2 整合素激活。有趣的是，与 CD28+T 细胞相比，ROS 依赖性 Ca 释放在致病关键 CD28null 亚群中更为普遍，而 β2 整合素激活经典途径（PKC、PI3K 和 PLC）的既定介质在两种 T细胞亚群。因此，对钙通量的干扰减弱了来自急性冠状动脉综合征患者的 CD28null T 细胞的自发粘附，并且钙离子载体消除了观察到的 CD28+ 和 CD28null T 细胞之间粘附特性的差异。同样，在外源性 ROS/H2O2 存在的情况下，这些 T 细胞亚群的粘附是无法区分的。一起，