Reactive oxidative species-modulated Ca2+ release regulates β2 integrin activation on CD4+ CD28null T cells of acute coronary syndrome patients

• Verfasst von: Samstag, Yvonne [VerfasserIn]
• Verfasst von: Bogert, Nicolai [VerfasserIn]
• Verfasst von: Wabnitz, Guido H. [VerfasserIn]
• Verfasst von: Din, Shabana [VerfasserIn]
• Verfasst von: Therre, Markus [VerfasserIn]
• Verfasst von: Leuschner, Florian [VerfasserIn]
• Verfasst von: Katus, Hugo [VerfasserIn]
• Verfasst von: Konstandin, Mathias [VerfasserIn]
• Titel: Reactive oxidative species-modulated Ca2+ release regulates β2 integrin activation on CD4+ CD28null T cells of acute coronary syndrome patients
• Verf.angabe: Yvonne Samstag, Nicolai V. Bogert, Guido H. Wabnitz, Shabana Din, Markus Therre, Florian Leuschner, Hugo A. Katus, and Mathias H. Konstandin
• E-Jahr: 2020
• Jahr: 16 September 2020
• Umfang: 11 S.
• Fussnoten: Im Titel sind 2+, +, null hochgestellt und 2 tiefgestellt ; Gesehen am 23.11.2020
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Bethesda, Md. : Soc., 1916
• Jahr Quelle: 2020
• Band/Heft Quelle: 205(2020), 8, Seite 2276-2286
• ISSN Quelle: 1550-6606
• DOI: doi:10.4049/jimmunol.2000327
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1740368037

Abstract

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.