Reactive oxidative species-modulated Ca2+ release regulates β2 integrin activation on CD4+ CD28null T cells of acute coronary syndrome patients
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 adh...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
16 September 2020
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| In: |
The journal of immunology
Year: 2020, Volume: 205, Issue: 8, Pages: 2276-2286 |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.2000327 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4049/jimmunol.2000327 Verlag, lizenzpflichtig, Volltext: https://www.jimmunol.org/content/205/8/2276 
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| Author Notes: | Yvonne Samstag, Nicolai V. Bogert, Guido H. Wabnitz, Shabana Din, Markus Therre, Florian Leuschner, Hugo A. Katus, and Mathias H. Konstandin |
| Summary: | 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. |
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| Item Description: | Im Titel sind 2+, +, null hochgestellt und 2 tiefgestellt Gesehen am 23.11.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.2000327 |