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

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.

Automated summary

Blood-brain barrier breakdown and immune cell infiltration are early markers of multiple sclerosis. Researchers have found that brain endothelial cells cross-present antigen to CD8(+) T cells, preventing their migration and initiating blood-brain barrier breakdown.