Brain endothelial antigen presentation detains CD8+ T cells at the blood-brain barrier leading to its breakdown

Aydin, S.; Pareja, J.; Schallenberg, V. M.; Klopstein, A.; Gruber, T.; Page, N.; Kaba, E.; Deutsch, U.; Johnson, A.; Schenk, M.; Merkler, D.; Engelhardt, B.

doi:10.1101/2021.10.12.464035

bioRxiv · 10.1101/2021.10.12.464035

Brain endothelial antigen presentation detains CD8+ T cells at the blood-brain barrier leading to its breakdown

Aydin, S.·Pareja, J.·Schallenberg, V. M.·Klopstein, A.·Gruber, T.·Page, N.·Kaba, E.·Deutsch, U.·Johnson, A.·Schenk, M.·Merkler, D.·Engelhardt, B.

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Abstract

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.

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Aydin, S., Pareja, J., Schallenberg, V. M., Klopstein, A., Gruber, T., Page, N., Kaba, E., Deutsch, U., Johnson, A., Schenk, M., Merkler, D., Engelhardt, B.. 2021-10-13. Brain endothelial antigen presentation detains CD8+ T cells at the blood-brain barrier leading to its breakdown. https://doi.org/10.1101/2021.10.12.464035

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