Abstract
Mechanisms mediating CD4+ T cell activation during hepatic ischemia-reperfusion (I/R) remain not fully understood. In this study, we tested the hypothesis that CD4+ T cells and Kupffer cells (KCs) interact during I/R via proinflammatory mediators causing reciprocal activation. In mice, accumulation of fluorescence-labeled CD4+ T cells was analyzed using intravital fluorescence microscopy in a sham-operated group, a group after warm lobar hepatic I/R (90/30–120min), and an additional I/R-group after depletion of KCs with GdCl3 (n = 6 each group). The I/R-induced accumulation of CD4+ T cells in sinusoids was significantly attenuated in mice undergoing depletion of KCs. To investigate whether KCs activate CD4+ T cells by releasing reactive oxygen species (ROS) and IL-6 as well as TNF-alpha, accumulation of CD4+ T cells was quantified in mice treated with the ROS scavenger glutathione, in IL-6-/- mice, and in wild-type mice after infusion of TNF-receptor-1-/- CD4+ T cells. Reduction of ROS and IL-6 as well as TNF-R1 deficiency attenuated postischemic CD4+ T cell accumulation (p < 0.05). Using flow cytometry we show in vitro that TNF-alpha and IL-6 are able to directly activate isolated CD4+ T cells and upregulate the expression of adhesion molecules on sinusoidal endothelial cells. Finally, we assessed whether CD4+ T cells might, in turn, trigger KC activation. As shown by an intravital microscopic analysis of the clearance kinetics of fluorescence-labeled latex beads, phagocytic activity of KCs was significantly depressed after I/R and this effect was enhanced in CD4-/- mice. In conclusion, this study demonstrates that KCs support the intrasinusoidal recruitment of CD4+ T cells during I/R. This effect is mediated by release of ROS and the cytokines TNF-alpha and IL-6, which together trigger activation of both CD4+ T cells and sinusoidal endothelial cells. In addition, CD4+ T cells seem to enhance the activation of KCs in the postischemic liver.
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© 2008 Springer Medizin Verlag Heidelberg
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Hanschen, M., Krombach, F., Khandoga, A. (2008). Reziproke Aktivierung von CD4+ T-Zellen und Kupffer-Zellen bei hepatischer Ischämie-Reperfusion. In: Arbogast, R., Schackert, H.K., Bauer, H. (eds) Chirurgisches Forum 2008. Deutsche Gesellschaft für Chirurgie, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-78833-1_77
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DOI: https://doi.org/10.1007/978-3-540-78833-1_77
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-78821-8
Online ISBN: 978-3-540-78833-1
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