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.

In this work, the presence of species of the slug family Milacidae in Switzerland was investigated by using the barcoding marker cytochrome c oxidase subunit I (COI) as well as traits of the body and the genital organs. Currently, three species of Tandonia living in Switzerland in established populations could be reported, i.e., T. rustica, T. budapestensis, and T. nigra. The three records of Milax gagates were re-investigated, but only for one of these records could the identification be reconfirmed. This species has currently no established and thriving population in Switzerland. For all species recorded, detailed descriptions of body morphology, genital anatomy, and distribution data are provided based on the investigated Swiss animals. An unknown pale colour morph of a Tandonia sp. from Canton Ticino could be identified as T. nigra, and the barcodes of T. nigra specimens were submitted to GenBank for the first time. The identity of the Italian and Austrian populations of T. nigra from the Bergamasque Alps and north Tirol is evaluated. Observations on details of the morphology of the genital organs in T. rustica vs. T. kusceri are discussed.

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) as in vitro model 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 neuroinflammation in 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.