In:
Nature Communications, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-05-30)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
2041-1723
DOI:
10.1038/s41467-023-38703-2
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2023
ZDB Id:
2553671-0