4724 total record number 96 records this year

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

Aydin, S;Pareja, J;Schallenberg, VM;Klopstein, A;Gruber, T;Page, N;Bouillet, E;Blanchard, N;Liblau, R;Körbelin, J;Schwaninger, M;Johnson, AJ;Schenk, M;Deutsch, U;Merkler, D;Engelhardt, B;

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.