Internalization and presentation of myelin antigens by the brain endothelium guides antigen-specific T cell migration
- VU university medical center, Netherlands
- VU University medical center, Netherlands
- VU University Medical Center, Netherlands
- ErasmusMC-Sophia Children's Hospital, Netherlands
Abstract
Trafficking of myelin-reactive CD4+ T-cells across the brain endothelium, an essential step in the pathogenesis of multiple sclerosis (MS), is suggested to be an antigen-specific process, yet which cells provide this signal is unknown. Here we provide direct evidence that under inflammatory conditions, brain endothelial cells (BECs) stimulate the migration of myelin-reactive CD4+ T-cells by acting as non-professional antigen presenting cells through the processing and presentation of myelin-derived antigens in MHC-II. Inflamed BECs internalized myelin, which was routed to endo-lysosomal compartment for processing in a time-dependent manner. Moreover, myelin/MHC-II complexes on inflamed BECs stimulated the trans-endothelial migration of myelin-reactive Th1 and Th17 2D2 cells, while control antigen loaded BECs did not stimulate T-cell migration. Furthermore, blocking the interaction between myelin/MHC-II complexes and myelin-reactive T-cells prevented T-cell transmigration. These results demonstrate that endothelial cells derived from the brain are capable of enhancing antigen-specific T cell recruitment.
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© 2016, Lopes Pinheiro et al.
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Internalization and presentation of myelin antigens by the brain endothelium guides antigen-specific T cell migration
eLife 5:e13149.
https://doi.org/10.7554/eLife.13149
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