Reactive Oxidative Species-Modulated Ca2+ Release Regulates β2 Integrin Activation on CD4+ CD28null T Cells of Acute Coronary Syndrome Patients.

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. PMID: 32938726 [PubMed - as supplied by publisher]
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Tags: J Immunol Source Type: research