Journal
HEPATOLOGY
Volume 43, Issue 2, Pages 306-315Publisher
WILEY
DOI: 10.1002/hep.21017
Keywords
-
Categories
Ask authors/readers for more resources
The mechanisms by which T cells contribute to the hepatic inflammation during antigen-independent ischemia/reperfusion (I/R) are not fully understood. We analyzed the recruitment of T cells in the postischemic hepatic microcirculation in vivo and tested the hypothesis that T cells interact with platelets and activate sinusoidal endothelial cells, resulting in microvascular dysfunction followed by tissue injury. Using intravital videofluorescence microscopy, we show in mice that warm hepatic I/R (90/30-140 min) induces accumulation and transendothelial migration of CD4(+), but not CD8(+) T cells in sinusoids during early reperfusion. Simultaneous visualization of fluorescence-labeled CD4(+) T cells and platelets showed that approximately 30% of all accumulated CD4(+) T cells were colocalized with platelets, suggesting an interaction between both cell types. Although interactions of CD4(+)/CD40L(-/-) T cells with CD40L(-/-) platelets in wild-type mice were slightly reduced, they were almost absent if CD4(+) T cells and platelets were from CD62P(-/-) mice. CD4 deficiency as well as CD40-CD40L and CD28-B7 disruption attenuated postischemic platelet adherence in the same manner as platelet inactivation with a glycoprotein IIb/IIIa antagonist and reduced neutrophil transmigration, sinusoidal perfusion failure, and transaminase activities. Treatment with an MHC class II antibody, however, did not affect I/R injury. In conclusion, we describe the type, kinetic, and microvascular localization of T cell recruitment in the postischemic liver. CD4(+) T cells interact with platelets in postischemic sinusoids, and this interaction is mediated by platelet CD62P. CD4(+) T cells activate endothelium, increase I/R-induced platelet adherence and neutrophil migration via CD40-CD40L and CD28-B7-dependent pathways, and aggravate microvascular/hepatocellular injury.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available