Antigen recognition detains CD8+ T cells at the blood-brain barrier and contributes to its breakdown

Sidar Aydin, Javier Pareja, Vivianne M. Schallenberg, Armelle Klopstein, Thomas Gruber, Nicolas Page, Elisa Bouillet, Nicolas Blanchard, Roland Liblau, Jakob Körbelin, Markus Schwaninger, Aaron J. Johnson, Mirjam Schenk, Urban Deutsch, Doron Merkler and Britta Engelhardt ()
Additional contact information
Sidar Aydin: University of Bern
Javier Pareja: University of Bern
Vivianne M. Schallenberg: University of Bern
Armelle Klopstein: University of Bern
Thomas Gruber: University of Bern
Nicolas Page: University and University Hospitals of Geneva
Elisa Bouillet: University of Bern
Nicolas Blanchard: University of Toulouse, CNRS, INSERM, UPS
Roland Liblau: University of Toulouse, CNRS, INSERM, UPS
Jakob Körbelin: University Medical Center Hamburg-Eppendorf
Markus Schwaninger: University of Lübeck
Aaron J. Johnson: Mayo Clinic
Mirjam Schenk: University of Bern
Urban Deutsch: University of Bern
Doron Merkler: University and University Hospitals of Geneva
Britta Engelhardt: University of Bern

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: Abstract Blood-brain barrier (BBB) breakdown and immune cell infiltration into the central nervous system (CNS) are early hallmarks of multiple sclerosis (MS). High numbers of CD8+ T cells are found in MS lesions, and antigen (Ag) presentation at the BBB has been proposed to promote CD8+ T cell entry into the CNS. Here, we show that brain endothelial cells process and cross-present Ag, leading to effector CD8+ T cell differentiation. Under physiological flow in vitro, endothelial Ag presentation prevented CD8+ T cell crawling and diapedesis resulting in brain endothelial cell apoptosis and BBB breakdown. Brain endothelial Ag presentation in vivo was limited due to Ag uptake by CNS-resident macrophages but still reduced motility of Ag-specific CD8+ T cells within CNS microvessels. MHC class I-restricted Ag presentation at the BBB during neuroinflammation thus prohibits CD8+ T cell entry into the CNS and triggers CD8+ T cell-mediated focal BBB breakdown.

Date: 2023
References: View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-38703-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38703-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-38703-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().