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.
Show 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.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Impact of SARS-CoV-2 vaccination on systemic immune responses in people living with HIV 94%
- Microglia and perivascular macrophages act as antigen presenting cells to promote CD8 T cell infiltration of the brain 94%
- MDSC depletion during immunization with heat-killed Mycobacterium tuberculosis increases protection against BCG infection. 94%
Similar papers in this journal
- Interoperability of RTN1A in dendrite dynamics and immune functions in human Langerhans cells 94%
- MHC class I and MHC class II reporter mice enable analysis of immune oligodendroglia in mouse models of multiple sclerosis 94%
- Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.