Rudolph, HenrietteHenrietteRudolphKlopstein, ArmelleArmelleKlopsteinGruber, Isabelle ManuelaIsabelle ManuelaGruberBlatti, ClaudiaClaudiaBlattiLyck, RuthRuthLyck0000-0002-6479-4837Engelhardt, BrittaBrittaEngelhardt0000-0003-3059-98462024-10-252024-10-252016-09https://boris-portal.unibe.ch/handle/20.500.12422/149751Although CD8(+) T cells have been implied in the pathogenesis of multiple sclerosis (MS), the molecular mechanisms mediating CD8(+) T-cell migration across the blood-brain barrier (BBB) into the central nervous system (CNS) are ill defined. Using in vitro live cell imaging, we directly compared the multistep extravasation of activated CD4(+) and CD8(+) T cells across primary mouse brain microvascular endothelial cells (pMBMECs) as a model for the BBB under physiological flow. Significantly higher numbers of CD8(+) than CD4(+) T cells arrested on pMBMECs under noninflammatory and inflammatory conditions. While CD4(+) T cells polarized and crawled prior to their diapedesis, the majority of CD8(+) T cells stalled and readily crossed the pMBMEC monolayer preferentially via a transcellular route. T-cell arrest and crawling were independent of G-protein-coupled receptor signaling. Rather, absence of endothelial ICAM-1 and ICAM-2 abolished increased arrest of CD8(+) over CD4(+) T cells and abrogated T-cell crawling, leading to the efficient reduction of CD4(+) , but to a lesser degree of CD8(+) , T-cell diapedesis across ICAM-1(null) /ICAM-2(-/-) pMBMECs. Thus, cellular and molecular mechanisms mediating the multistep extravasation of activated CD8(+) T cells across the BBB are distinguishable from those involved for CD4(+) T cells.enAdhesionBlood-brain barrierCrawlingDiapedesisStallingT cells600 - Technology::610 - Medicine & healtharticle10.7892/boris.953592733880610.1002/eji.201546251