Foxp3-independent loss of regulatory CD4+ T-cell suppressive capacities induced by self-deprivation

Authors

  • Arnaud Delpoux,

    1. CNRS UMR8104, Cochin Hospital, Paris, France
    2. INSERM U567, Cochin Hospital, Paris, France
    3. Paris Descartes University, Cochin Hospital, Paris, France
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  • Maud Poitrasson-Rivière,

    1. CNRS UMR8104, Cochin Hospital, Paris, France
    2. INSERM U567, Cochin Hospital, Paris, France
    3. Paris Descartes University, Cochin Hospital, Paris, France
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  • Armelle Le Campion,

    1. CNRS UMR8104, Cochin Hospital, Paris, France
    2. INSERM U567, Cochin Hospital, Paris, France
    3. Paris Descartes University, Cochin Hospital, Paris, France
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  • Arnaud Pommier,

    1. CNRS UMR8104, Cochin Hospital, Paris, France
    2. INSERM U567, Cochin Hospital, Paris, France
    3. Paris Descartes University, Cochin Hospital, Paris, France
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  • Philippe Yakonowsky,

    1. CNRS UMR8104, Cochin Hospital, Paris, France
    2. INSERM U567, Cochin Hospital, Paris, France
    3. Paris Descartes University, Cochin Hospital, Paris, France
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  • Sébastien Jacques,

    1. CNRS UMR8104, Cochin Hospital, Paris, France
    2. INSERM U567, Cochin Hospital, Paris, France
    3. Paris Descartes University, Cochin Hospital, Paris, France
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  • Franck Letourneur,

    1. CNRS UMR8104, Cochin Hospital, Paris, France
    2. INSERM U567, Cochin Hospital, Paris, France
    3. Paris Descartes University, Cochin Hospital, Paris, France
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  • Clotilde Randriamampita,

    1. CNRS UMR8104, Cochin Hospital, Paris, France
    2. INSERM U567, Cochin Hospital, Paris, France
    3. Paris Descartes University, Cochin Hospital, Paris, France
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  • Bruno Lucas,

    Corresponding author
    1. CNRS UMR8104, Cochin Hospital, Paris, France
    2. INSERM U567, Cochin Hospital, Paris, France
    3. Paris Descartes University, Cochin Hospital, Paris, France
    • Dr. Bruno Lucas, Cochin Hospital, 75014 Paris, France

      Fax: +33-1-40516535

      e-mail: bruno.lucas@inserm.fr

      Additional correspondence: Dr. Cédric Auffray, Cochin Hospital, 75014 Paris, France

      Fax: +33-1-40516535

      e-mail: bruno.lucas@inserm.fr

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    • These authors contributed equally to this work.

  • and Cédric Auffray

    Corresponding author
    1. CNRS UMR8104, Cochin Hospital, Paris, France
    2. INSERM U567, Cochin Hospital, Paris, France
    3. Paris Descartes University, Cochin Hospital, Paris, France
    • Dr. Bruno Lucas, Cochin Hospital, 75014 Paris, France

      Fax: +33-1-40516535

      e-mail: bruno.lucas@inserm.fr

      Additional correspondence: Dr. Cédric Auffray, Cochin Hospital, 75014 Paris, France

      Fax: +33-1-40516535

      e-mail: bruno.lucas@inserm.fr

    Search for more papers by this author
    • These authors contributed equally to this work.


Abstract

In the periphery, Foxp3 expression is considered sufficient to maintain natural regulatory CD4+ T-cell suppressive function. In this study, we challenge this model. Indeed, in mouse chimeras in which major histocompatibility complex (MHC) class II expression is restricted to the thymus, peripheral regulatory CD4+ T cells lack suppressive activity. In addition, regulatory CD4+ T cells recovered 5 days after transfer into recipient mice lacking expression of MHC class II molecules (self-deprived) are unable to inhibit the proliferative response of conventional CD4+ T cells both in vitro and in vivo. Disruption of TCR/MHC class II interactions rapidly leads to alterations in the regulatory CD4+ T-cell phenotype, the ability to respond to stimulation and to produce interleukin-10, and the transcriptional signature. Interestingly, self-deprivation does not affect Foxp3 expression indicating that in regulatory CD4+ T cells, self-recognition induces unique transcriptional and functional features that do not rely on Foxp3 expression.

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