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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Normalized velocity of T cell blasts. Objective assessment of T lymphobl...
Normalized velocity of T cell blasts. Objective assessment of T lymphoblast/endothelial interaction was obtained by comparing the velocity distribution of T cells observed in vessels of comparable size. For the control group, 198 cells in eight venules of two mice, for the anti–α4-group, 440 cells in 22 venules of four mice, and for the anti–VCAM-1 group 236 cells in 15 venules of three mice were analyzed. Vcrit, the velocity of an idealized noninteracting T cell blast, was calculated as described in Methods. Five percent of circulating T cells were transiently captured at the vascular wall (a, c). Blocking α4-integrin (a) or VCAM-1 (c) resulted in a significantly reduced number of captured T cells (a, c). Lack of T lymphoblast rolling is demonstrated by the lack of T cells traveling at velocities below Vcrit (b, d).