1. Antigen recognition detains CD8+ T cells at the blood-brain barrier and contributes to its breakdown.
- Author
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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, and Engelhardt, Britta
- Subjects
BLOOD-brain barrier ,T cells ,IMMUNE recognition ,T cell receptors ,T cell differentiation ,CENTRAL nervous system ,ENDOTHELIAL cells - 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. Blood-brain barrier (BBB) breakdown and immune cell infiltration into the central nervous system are early hallmarks of multiple sclerosis. Here, the authors demonstrate that brain endothelial cells cross-present antigen to CD8+ T cells, thereby preventing their migration and initiating BBB breakdown. [ABSTRACT FROM AUTHOR]- Published
- 2023
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