T-cell migration across the blood-brain barrier (BBB) is a crucial step in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (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 wild-type or PSGL-1-/- PLP-specific T cells in inflamed spinal cord microvessels of wild-type 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.
Sathiyanadan K, Coisne C, Enzmann G, Deutsch U, Engelhardt B. PSGL-1 and E/P-selectins are essential for T-cell rolling in inflamed CNS microvessels but dispensable for initiation of EAE. Eur J Immunol. 2014 Apr. doi: 10.1002/eji.201344214. [Epub ahead of print
The way cells exit the blood was first seen by looking at cells (neutrophils) coming out of blood in the gut as the vessels were easy to dissect and put under a microscope. There was seen that blood cells are slowed down they contact selectins (carbohydrate molecules) and start rolling before they tether and migrate. However, this study shows that they don’t need to roll to cell into the brain.