| First Author | Aydin S | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 3106 |
| PubMed ID | 37253744 | Mgi Jnum | J:337243 |
| Mgi Id | MGI:7487447 | Doi | 10.1038/s41467-023-38703-2 |
| Citation | Aydin S, et al. (2023) Antigen recognition detains CD8(+) T cells at the blood-brain barrier and contributes to its breakdown. Nat Commun 14(1):3106 |
| abstractText | 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. |
