Aydin, Sidar; Pareja, Javier; Schallenberg, Vivianne M; Klopstein, Armelle; Gruber, Thomas; Page, Nicolas; Bouillet, Elisa; Blanchard, Nicolas; Liblau, Roland; Körbelin, Jakob; Schwaninger, Markus; Johnson, Aaron J; Schenk, Mirjam; Deutsch, Urban; Merkler, Doron; Engelhardt, Britta (2023). Antigen recognition detains CD8+ T cells at the blood-brain barrier and contributes to its breakdown. Nature communications, 14(1), p. 3106. Nature Publishing Group 10.1038/s41467-023-38703-2
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute 04 Faculty of Medicine > Service Sector > Institute of Pathology |
UniBE Contributor: |
Aydin, Sidar, Pareja Román, Javier, Klopstein, Armelle, Gruber, Thomas, Bouillet, Elisa Catherine, Schenk, Mirjam, Deutsch, Urban, Engelhardt, Britta |
Subjects: |
600 Technology > 610 Medicine & health 500 Science > 570 Life sciences; biology |
ISSN: |
2041-1723 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
31 May 2023 10:27 |
Last Modified: |
04 Jun 2023 02:27 |
Publisher DOI: |
10.1038/s41467-023-38703-2 |
PubMed ID: |
37253744 |
BORIS DOI: |
10.48350/183045 |
URI: |
https://boris.unibe.ch/id/eprint/183045 |
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