α4-integrin-VCAM-1 binding mediates G protein–independent capture of encephalitogenic T cell blasts to CNS white matter microvessels
Peter Vajkoczy, Melanie Laschinger, Britta Engelhardt
Peter Vajkoczy, Melanie Laschinger, Britta Engelhardt
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α4-integrin-VCAM-1 binding mediates G protein–independent capture of encephalitogenic T cell blasts to CNS white matter microvessels

Abstract

Direct in vivo evidence is still lacking for α4-integrin–mediated T cell interaction with VCAM-1 on blood-brain barrier–endothelium in experimental autoimmune encephalomyelitis (EAE). To investigate a possible α4-integrin–mediated interaction of encephalitogenic T cell blasts with VCAM-1 on the blood-brain barrier white matter endothelium in vivo, we have developed a novel spinal cord window preparation that enabled us to directly visualize CNS white matter microcirculation by intravital fluorescence videomicroscopy. Our study provides the first in vivo evidence that encephalitogenic T cell blasts interact with the spinal cord white matter microvasculature without rolling and that α4-integrin mediates the G protein–independent capture and subsequently the G protein–dependent adhesion strengthening of T cell blasts to microvascular VCAM-1.

Authors

Peter Vajkoczy, Melanie Laschinger, Britta Engelhardt

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T lymphoblast/endothelium interaction within spinal white matter postcap...
T lymphoblast/endothelium interaction within spinal white matter postcapillary venules during cell infusion. (a) Postcapillary venular segment before cell infusion after contrast enhancement of spinal microvasculature using FITC-dextran150. Arrows indicate direction of microvascular blood flow. (b–e) Intravital microscopic sequence of two Cell Tracker Orange–labeled T lymphocytes (1 and 2) over 0.24 seconds within the identical postcapillary segments indicated in a. Cells either lacked interaction with endothelium or were captured to endothelium without prior rolling. Bar, 100 μm.