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

Eur J Immunol. 2006 Nov;36(11):2981-92. doi: 10.1002/eji.200636207.

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-beta, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / analysis
  • Dermatitis, Contact / immunology*
  • Dermatitis, Contact / prevention & control
  • Epithelium / drug effects
  • Epithelium / immunology
  • Haptens / pharmacology
  • Immune Tolerance*
  • Interleukin-10 / analysis
  • Interleukin-10 / metabolism*
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Leukocyte Rolling / immunology*
  • Leukocytes / drug effects
  • Leukocytes / immunology
  • Male
  • T-Lymphocytes, Regulatory / chemistry
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / transplantation

Substances

  • CD4 Antigens
  • Haptens
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-10