Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation

  1. Antonio P Baptista
  2. Ramon Roozendaal
  3. Rogier M Reijmers
  4. Jasper J Koning
  5. Wendy W Unger
  6. Mascha Greuter
  7. Eelco D Keuning
  8. Rosalie Molenaar
  9. Gera Goverse
  10. Marlous M S Sneeboer
  11. Joke M M den Haan
  12. Marianne Boes
  13. Reina E Mebius  Is a corresponding author
  1. Vrije Universiteit Medical Center, Netherlands
  2. Janssen Center of Excellence for Immunoprophylaxis, Netherlands
  3. University Medical Center Utrecht, Netherlands

Abstract

Non-hematopoietic lymph node stromal cells shape immunity by inducing MHC-I-dependent deletion of self-reactive CD8+ T cells and MHC-II-dependent anergy of CD4+ T cells. Here, we show that MHC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence. In the absence of MHC-II expression in lymph node transplants, i.e. on lymph node stromal cells, CD4+ as well as CD8+ T cells became activated, ultimately resulting in transplant rejection. MHC-II self-antigen presentation by lymph node stromal cells allowed the non-proliferative maintenance of antigen-specific Tregs and constrained antigen-specific immunity. Altogether, our results reveal a novel mechanism by which lymph node stromal cells regulate peripheral immunity.

Article and author information

Author details

  1. Antonio P Baptista

    Vrije Universiteit Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  2. Ramon Roozendaal

    Janssen Center of Excellence for Immunoprophylaxis, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Rogier M Reijmers

    Vrije Universiteit Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Jasper J Koning

    Vrije Universiteit Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Wendy W Unger

    Vrije Universiteit Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Mascha Greuter

    Vrije Universiteit Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Eelco D Keuning

    Vrije Universiteit Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  8. Rosalie Molenaar

    Vrije Universiteit Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  9. Gera Goverse

    Vrije Universiteit Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  10. Marlous M S Sneeboer

    Vrije Universiteit Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  11. Joke M M den Haan

    Vrije Universiteit Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  12. Marianne Boes

    University Medical Center Utrecht, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  13. Reina E Mebius

    Vrije Universiteit Medical Center, Amsterdam, Netherlands
    For correspondence
    r.mebius@vumc.nl
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All animal experiments were reviewed and approved by the Vrije University Scientific and Ethics Committees (protocols MCB09-35, MCB10-01 and MCB13-06). All surgery was performed under xylazine and ketamine anesthesia.

Copyright

© 2014, Baptista 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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  1. Antonio P Baptista
  2. Ramon Roozendaal
  3. Rogier M Reijmers
  4. Jasper J Koning
  5. Wendy W Unger
  6. Mascha Greuter
  7. Eelco D Keuning
  8. Rosalie Molenaar
  9. Gera Goverse
  10. Marlous M S Sneeboer
  11. Joke M M den Haan
  12. Marianne Boes
  13. Reina E Mebius
(2014)
Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation
eLife 3:e04433.
https://doi.org/10.7554/eLife.04433

Share this article

https://doi.org/10.7554/eLife.04433

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