1. Immunology and Inflammation
  2. Microbiology and Infectious Disease
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The viral context instructs the redundancy of costimulatory pathways in driving CD8+ T cell expansion

  1. Suzanne PM Welten
  2. Anke Redeker
  3. Kees LMC Franken
  4. Jennifer D Oduro
  5. Ferry Ossendorp
  6. Luka Čičin-Šain
  7. Cornelis JM Melief
  8. Peter Aichele
  9. Ramon Arens  Is a corresponding author
  1. Leiden University Medical Center, Netherlands
  2. Helmholtz-Zentrum für Infektionsforschung GmbH, Germany
  3. University of Freiburg, Germany
Research Article
  • Cited 29
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Cite this article as: eLife 2015;4:e07486 doi: 10.7554/eLife.07486

Abstract

Signals delivered by costimulatory molecules are implicated in driving T cell expansion. The requirements for these signals, however, vary from dispensable to essential in different infections. We examined the underlying mechanisms of this differential T cell costimulation dependence and found that the viral context determined the dependence on CD28/B7-mediated costimulation for expansion of naive and memory CD8+ T cells, indicating that the requirement for costimulatory signals is not imprinted. Notably, related to the high-level costimulatory molecule expression induced by LCMV, CD28/B7-mediated costimulation was dispensable for accumulation of LCMV-specific CD8+ T cells because of redundancy with the costimulatory pathways induced by TNF receptor family members (i.e. CD27, OX40, and 4-1BB). Type I IFN signaling in viral-specific CD8+ T cells is slightly redundant with costimulatory signals. These results highlight that pathogen-specific conditions differentially and uniquely dictate the utilization of costimulatory pathways allowing shaping of effector and memory antigen-specific CD8+ T cell responses.

Article and author information

Author details

  1. Suzanne PM Welten

    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  2. Anke Redeker

    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Kees LMC Franken

    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Jennifer D Oduro

    Department for Vaccinology/Immune Aging and Chronic Infection, Helmholtz-Zentrum für Infektionsforschung GmbH, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Ferry Ossendorp

    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Luka Čičin-Šain

    Department for Vaccinology/Immune Aging and Chronic Infection, Helmholtz-Zentrum für Infektionsforschung GmbH, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Cornelis JM Melief

    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  8. Peter Aichele

    Department of Medical Microbiology and Hygiene, Institute of Immunology, University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Ramon Arens

    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
    For correspondence
    R.Arens@lumc.nl
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Animal experiments were approved by the Animal Experiments Committee of the LUMC (reference numbers: 12006, 13150, 14046 and 14066) and performed according to the recommendations and guidelines set by the LUMC and by the Dutch Experiments on Animals Act that serves the implementation of 'Guidelines on the protection of experimental animals' by the Council of Europe.

Reviewing Editor

  1. Satyajit Rath, National Institute of Immunology, India

Publication history

  1. Received: March 15, 2015
  2. Accepted: August 10, 2015
  3. Accepted Manuscript published: August 11, 2015 (version 1)
  4. Version of Record published: September 3, 2015 (version 2)

Copyright

© 2015, Welten 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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