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

Rudolph, Henriette; Klopstein, Armelle; Gruber, Isabelle Manuela; Blatti, Claudia; Lyck, Ruth; Engelhardt, Britta (2016). Postarrest stalling rather than crawling favors CD8(+) over CD4(+) T-cell migration across the blood-brain barrier under flow in vitro. European journal of immunology, 46(9), pp. 2187-2203. Wiley-VCH 10.1002/eji.201546251

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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-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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Klopstein, Armelle; Gruber, Isabelle Manuela; Blatti, Claudia; Lyck, Ruth and Engelhardt, Britta

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0014-2980

Publisher:

Wiley-VCH

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

22 May 2017 12:07

Last Modified:

23 May 2017 09:12

Publisher DOI:

10.1002/eji.201546251

PubMed ID:

27338806

Uncontrolled Keywords:

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

BORIS DOI:

10.7892/boris.95359

URI:

https://boris.unibe.ch/id/eprint/95359

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