1. Immunology and Inflammation
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CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection

  1. Michelle A Linterman  Is a corresponding author
  2. Alice E Denton
  3. Devina P Divekar
  4. Ilona Zvetkova
  5. Leanne Kane
  6. Cristina Ferreira
  7. Marc Veldhoen
  8. Simon Clare
  9. Gordon Dougan
  10. Marion Espéli
  11. Kenneth G C Smith
  1. Babraham Institute, United Kingdom
  2. University of Cambridge, United Kingdom
  3. University of East Anglia, United Kingdom
  4. University of Cambridge Metabolic Research Laboratories, United Kingdom
  5. Wellcome Trust Sanger Institute, United Kingdom
  6. UMR-S996, LabEx LERMIT, France
  7. University of Cambridge School of Clinical Medicine, United Kingdom
Research Article
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Cite this article as: eLife 2014;3:e03180 doi: 10.7554/eLife.03180

Abstract

The costimulatory molecule CD28 is essential for activation of helper T cells. Despite this critical role, it is not known whether CD28 has functions in maintaining T cell responses following activation. To determine the role for CD28 after T cell priming we generated a strain of mice where CD28 is removed from CD4+ T cells after priming. We show that continued CD28 expression is important for effector CD4+ T cells following infection; maintained CD28 is required for the expansion of T helper type 1 cells, and for the differentiation and maintenance of T follicular helper cells during viral infection. Persistent CD28 is also required for clearance of the bacterium Citrobacter rodentium from the gastrointestinal tract. Together, this study demonstrates that CD28 persistence is required for helper T cell polarization in response to infection, describing a novel function for CD28 that is distinct from its role in T cell priming.

Article and author information

Author details

  1. Michelle A Linterman

    Babraham Institute, Cambridge, United Kingdom
    For correspondence
    Michelle.Linterman@babraham.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  2. Alice E Denton

    University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Devina P Divekar

    University of East Anglia, Norwich, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Ilona Zvetkova

    University of Cambridge Metabolic Research Laboratories, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Leanne Kane

    Wellcome Trust Sanger Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Cristina Ferreira

    Babraham Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Marc Veldhoen

    Babraham Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Simon Clare

    Wellcome Trust Sanger Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Gordon Dougan

    Wellcome Trust Sanger Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Marion Espéli

    UMR-S996, LabEx LERMIT, Clamart, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Kenneth G C Smith

    University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All experiments were performed according to the regulations of the UK Home Office Scientific Procedures Act (1986) under the UK Home Office license PPL 80/2438, or PPL 80/2596.

Reviewing Editor

  1. Fiona M Powrie, Oxford University, United Kingdom

Publication history

  1. Received: April 29, 2014
  2. Accepted: October 24, 2014
  3. Accepted Manuscript published: October 27, 2014 (version 1)
  4. Version of Record published: November 25, 2014 (version 2)

Copyright

© 2014, Linterman 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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