Postarrest stalling rather than crawling favors CD8+ over CD4+ T-cell migration across the blood-brain barrier under flow in vitro
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 mult...
Gespeichert in:
| 1. Verfasser: | |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
24 June 2016
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| In: |
European journal of immunology
Year: 2016, Jahrgang: 46, Heft: 9, Pages: 2187-2203 |
| ISSN: | 1521-4141 |
| DOI: | 10.1002/eji.201546251 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1002/eji.201546251 Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.201546251 
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| Verfasserangaben: | Henriette Rudolph, Armelle Klopstein, Isabelle Gruber, Claudia Blatti, Ruth Lyck and Britta Engelhardt |
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| 520 | |a 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. | ||
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