Encephalitogenic T cells use LFA-1 for transendothelial migration but not during capture and initial adhesion strengthening in healthy spinal cord microvessels in vivo.
LFA-1 on the surface of encephalitogenic T cells has been suggested to be involved in the pathogenesis of experimental autoimmune encephalomyelitis. By applying a novel technique of intravital fluorescence microscopy that enables us to visualize the interaction of circulating encephalitogenic T lymphoblasts within the healthy spinal cord white matter microvasculature in vivo, we investigated the possible involvement of LFA-1 on circulating encephalitogenic T cells in their multi-step interaction with the blood-brain barrier endothelium in vivo. LFA-1 was found to mediate neither the G-protein-independent capture nor the G-protein-dependent initial adhesion strengthening of encephalitogenic T cell blasts within spinal cord microvessels. In contrast, blocking of LFA-1 on encephalitogenic T lymphoblasts resulted in a significantly reduced number of T cells firmly adhering within spinal cord microvessels 2 h after injection and in a significantly reduced number of T cells subsequently migrating across the vascular wall into the spinal cord parenchyme. Our study provides the first direct evidence that encephalitogenic T cells use LFA-1 for transendothelial migration but not for capture and initial adhesion in spinal cord microvessels in vivo.
Laschinger
Melanie
M
Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany.
Vajkoczy
Peter
P
Engelhardt
Britta
B
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D004730:Endothelium, Vascular / Q000276:immunology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D051379:Mice; D008833:Microcirculation / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology*
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D019204:GTP-Binding Proteins