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Scientific article
Open access
English

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

Published inNature communications, vol. 14, no. 1, 3106
Publication date2023-05-30
First online date2023-05-30
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 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.

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Keywords
  • Humans
  • Blood-Brain Barrier / metabolism
  • CD8-Positive T-Lymphocytes
  • Endothelial Cells / metabolism
  • Central Nervous System / metabolism
  • Multiple Sclerosis
  • Histocompatibility Antigens Class I / metabolism
Citation (ISO format)
AYDIN, Sidar et al. Antigen recognition detains CD8+ T cells at the blood-brain barrier and contributes to its breakdown. In: Nature communications, 2023, vol. 14, n° 1, p. 3106. doi: 10.1038/s41467-023-38703-2
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ISSN of the journal2041-1723
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