1. Immunology and Inflammation
  2. Neuroscience
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Internalization and presentation of myelin antigens by the brain endothelium guides antigen-specific T cell migration

  1. Melissa A Lopes Pinheiro
  2. Alwin Kamermans
  3. Juan J Garcia-Vallejo
  4. Bert van het Hof
  5. Laura Wierts
  6. Tom O'Toole
  7. Daniël Boeve
  8. Marleen Verstege
  9. Susanne MA van der Pol
  10. Yvette van Kooyk
  11. Helga E de Vries
  12. Wendy WJ Unger  Is a corresponding author
  1. VU university medical center, Netherlands
  2. VU University medical center, Netherlands
  3. VU University Medical Center, Netherlands
  4. ErasmusMC-Sophia Children's Hospital, Netherlands
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Cite this article as: eLife 2016;5:e13149 doi: 10.7554/eLife.13149

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.

Article and author information

Author details

  1. Melissa A Lopes Pinheiro

    Department of Molecular Cell Biology and Immunology, VU university medical center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  2. Alwin Kamermans

    Department of Molecular Cell Biology and Immunology, VU university medical center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Juan J Garcia-Vallejo

    Department of Molecular Cell Biology and Immunology, VU university medical center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Bert van het Hof

    Department of Molecular Cell Biology and Immunology, VU university medical center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Laura Wierts

    Department of Molecular Cell Biology and Immunology, VU university medical center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Tom O'Toole

    Department of Molecular Cell Biology and Immunology, VU University medical center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Daniël Boeve

    Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  8. Marleen Verstege

    Department of Molecular Cell Biology and Immunology, VU University medical center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  9. Susanne MA van der Pol

    Department of Molecular Cell Biology and Immunology, VU University medical center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  10. Yvette van Kooyk

    Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  11. Helga E de Vries

    Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  12. Wendy WJ Unger

    Department of Pediatrics, ErasmusMC-Sophia Children's Hospital, Rotterdam, Netherlands
    For correspondence
    w.unger@erasmusmc.nl
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Gary L Westbrook, Vollum Institute, United States

Publication history

  1. Received: November 19, 2015
  2. Accepted: June 22, 2016
  3. Accepted Manuscript published: June 23, 2016 (version 1)
  4. Version of Record published: July 25, 2016 (version 2)

Copyright

© 2016, Lopes Pinheiro et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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