CD4+CD25+ regulatory T cells suppress contact hypersensitivity reactions by blocking influx of effector T cells into inflamed tissue

Authors

  • Sabine Ring Dr.,

    Corresponding author
    1. Department of Dermatology, University of Heidelberg, Heidelberg, Germany
    • Department of Dermatology, University of Heidelberg, Vossstr. 11, 69115 Heidelberg, Germany, Fax: +49(0)6221-561617
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    • The two first authors and two senior authors contributed equally to this work

  • Stephan C. Schäfer,

    1. Institut Universitaire de Pathologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
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    • The two first authors and two senior authors contributed equally to this work

  • Karsten Mahnke,

    1. Department of Dermatology, University of Heidelberg, Heidelberg, Germany
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  • Hans-Anton Lehr,

    1. Institut Universitaire de Pathologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
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    • The two first authors and two senior authors contributed equally to this work

  • Alexander H. Enk

    1. Department of Dermatology, University of Heidelberg, Heidelberg, Germany
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    • The two first authors and two senior authors contributed equally to this work


Abstract

CD4+CD25+ regulatory T cells (Treg) exert suppressive functions on effector T cells in vitro and in vivo. However, the exact cellular events that mediate this inhibitory action remain largely unclear. To elucidate these events, we used intravital microscopy in a model of contact hypersensitivity (CHS) and visualized the leukocyte-endothelium interaction at the site of antigen challenge in awake C57BL/6 mice. Injection of Treg i.v. into sensitized mice at the time of local hapten challenge significantly inhibited rolling and adhesion of endogenous leukocytes to the endothelium. A similar inhibition of leukocyte recruitment could be recorded after injection of Treg-derived tissue culture supernatant. Thus, these data indicate that soluble factors may account for the suppressive effects. Accordingly we found that IL-10, but not TGF-β, was produced by Treg upon stimulation and that addition of anti-IL-10 antibodies abrogated the suppressive effects of Treg and tissue culture supernatant in CHS reactions. Moreover, CD4+CD25+ T cells isolated from IL-10–/– mice were not able to suppress the immune response induced by hapten treatment in C57BL/6 mice. In conclusion, our data suggest that cytokine-dependent rather than cell-cell contact-dependent mechanisms play a pivotal role in the suppression of CHS reactions by Treg in vivo.

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