title: PSGL-1 and E/P-selectins are essential for T-cell rolling in inflamed CNS microvessels but dispensable for initiation of EAE.
abstract: T-cell migration across the blood-brain barrier is a crucial step in the pathogenesis of EAE, an animal model for MS. Live cell imaging studies demonstrated that P-selectin glycoprotein ligand-1 (PSGL-1) and its endothelial ligands E- and P-selectin mediate the initial rolling of T cells in brain vessels during EAE. As functional absence of PSGL-1 or E/P-selectins does not result in ameliorated EAE, we speculated that T-cell entry into the spinal cord is independent of PSGL-1 and E/P-selectin. Performing intravital microscopy, we observed the interaction of WT or PSGL-1(-/-) proteolipid protein-specific T cells in inflamed spinal cord microvessels of WT or E/P-selectin(-/-) SJL/J mice during EAE. T-cell rolling but not T-cell capture was completely abrogated in the absence of either PSGL-1 or E- and P-selectin, resulting in a significantly reduced number of T cells able to firmly adhere in the inflamed spinal cord microvessels, but did not lead to reduced T-cell invasion into the CNS parenchyma. Thus, PSGL-1 interaction with E/P-selectin is essential for T-cell rolling in inflamed spinal cord microvessels during EAE. Taken together with previous observations, our findings show that T-cell rolling is not required for successful T-cell entry into the CNS and initiation of EAE.
authors.affiliation: Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Karthik
authors.initials: K
authors.lastname: Sathiyanadan
authors.forename: Caroline
authors.initials: C
authors.lastname: Coisne
authors.forename: Gaby
authors.initials: G
authors.lastname: Enzmann
authors.forename: Urban
authors.initials: U
authors.lastname: Deutsch
authors.forename: Britta
authors.initials: B
authors.lastname: Engelhardt
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D019040:E-Selectin / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D055806:Microvessels / Q000276:immunology*; D019007:P-Selectin / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D019040:E-Selectin; D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein
keywords: Blood-brain barrier; Experimental autoimmune encephalomyelitis; P-selectin; P-selectin glycoprotein ligand-1; T-cell rolling