Brain endothelial antigen presentation detains CD8+T cells at the blood-brain barrier leading 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 was proposed to promote CD8+T-cell entry into the CNS. Employing live cell imaging and primary mouse brain microvascular endothelial cells (pMBMECs) asin vitromodel of the BBB and a mouse model of CNS autoimmunity, we here show that pMBMECs process and present antigens leading to effector CD8+T-cell differentiation. Under physiological flow, endothelial Ag-presentation prohibited CD8+T-cell crawling and diapedesis leading to pMBMEC apoptosis. Reduced motility of Ag-specific CD8+T cells was also observed in CNS microvessels in neuroinflammationin vivo.Luminal MHC class I Ag-presentation at the BBB thus prohibits CD8+T-cell entry into the CNS and rather triggers CD8+T cell mediated focal BBB breakdown.