Postarrest stalling rather than crawling favors CD8+ over CD4+ T-cell migration across the blood-brain barrier under flow in vitro

• Verfasst von: Rudolph, Henriette [VerfasserIn]
• Titel: Postarrest stalling rather than crawling favors CD8+ over CD4+ T-cell migration across the blood-brain barrier under flow in vitro
• Verf.angabe: Henriette Rudolph, Armelle Klopstein, Isabelle Gruber, Claudia Blatti, Ruth Lyck and Britta Engelhardt
• E-Jahr: 2016
• Jahr: 24 June 2016
• Umfang: 17 S.
• Fussnoten: Gesehen am 28.01.2019 ; Im Titel sind CD8+ und CD4+ mit dem Pluszeichen geschrieben
• Titel Quelle: Enthalten in: European journal of immunology
• Ort Quelle: Weinheim : Wiley-VCH, 1971
• Jahr Quelle: 2016
• Band/Heft Quelle: 46(2016), 9, Seite 2187-2203
• ISSN Quelle: 1521-4141
• DOI: doi:10.1002/eji.201546251
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adhesion
• Sach-SW: Blood-brain barrier
• Sach-SW: Crawling
• Sach-SW: Diapedesis
• Sach-SW: Stalling
• Sach-SW: T cells
• K10plus-PPN: 1586634348

Abstract

Although 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-1null/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.