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

作者：Rudolph Henriette; Klopstein Armelle; Gruber Isabelle; Blatti Claudia; Lyck Ruth; Engelhardt Britta^*

来源：European Journal of Immunology, 2016, 46(9): 2187-2203.

DOI：10.1002/eji.201546251

• Adhesion
• Blood-brain barrier
• Crawling
• Diapedesis
• Stalling
• T cells

Although CD8(+) Tcells 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(+) Tcells across primary mouse brain microvascular endothelial cells (pMBMECs) as a model for the BBB under physiological flow. Significantly higher numbers of CD8(+) than CD4(+) Tcells arrested on pMBMECs under noninflammatory and inflammatory conditions. While CD4(+) Tcells polarized and crawled prior to their diapedesis, the majority of CD8(+) Tcells 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(+) Tcells 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(+) Tcells across the BBB are distinguishable from those involved for CD4(+) Tcells.

• 出版日期2016-9