IL-12-mediated STAT4 signaling and TCR signal strength cooperate in the induction of CD40L in human and mouse CD8+ T cells

Authors

  • Regina Stark,

    1. Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Berlin, Germany
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  • Anett Hartung,

    1. Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Berlin, Germany
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  • Dietmar Zehn,

    1. Swiss Vaccine Research Institute (SVRI), Epalinges, Switzerland
    2. Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland
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  • Marco Frentsch,

    1. Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Berlin, Germany
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  • Andreas Thiel

    Corresponding author
    • Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Berlin, Germany
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Full correspondence: Prof. Andreas Thiel, Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, CVK Charité University Medicine, Föhrerstr. 15, 13533 Berlin, Germany

Fax: +49-30-450539955

e-mail: andreas.thiel@charite.de

See accompanying Commentary by Nolte and van Lier

Abstract

CD40L is one of the key molecules bridging the activation of specific T cells and the maturation of professional and nonprofessional antigen-presenting cells including B cells. CD4+ T cells have been regarded as the major T-cell subset that expresses CD40L upon cognate activation; however, we demonstrate here that a putative CD8+ helper T-cell subset expressing CD40L is induced in human and murine CD8+ T cells in vitro and in mice immunized with antigen-pulsed dendritic cells. IL-12 and STAT4-mediated signaling was the major instructive cytokine signal boosting the ability of CD8+ T cells to express CD40L both in vitro and in vivo. Additionally, TCR signaling strength modulated CD40L expression in CD8+ T cells after primary differentiation in vitro as well as in vivo. The induction of CD40L in CD8+ T cells regulated by IL-12 and TCR signaling may enable CD8+ T cells to respond autonomously of CD4+ T cells. Thus, we propose that under proinflammatory conditions, a self-sustaining positive feedback loop could facilitate the efficient priming of T cells stimulated by high affinity peptide displaying APCs.

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