Article: article from journal or magazin.
CD4+ CD25+ regulatory T cells suppress contact hypersensitivity reactions by blocking influx of effector T cells into inflamed tissue
European Journal of Immunology
PT - Journal Article PT - Research Support, Non-U.S. Gov't
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
Animals/Antigens,CD4/analysis/Dermatitis,Contact/immunology/prevention & control/Epithelium/drug effects/Haptens/pharmacology/Immune Tolerance/Interleukin-10/metabolism/Interleukin-2 Receptor alpha Subunit/Leukocyte Rolling/Leukocytes/Male/T-Lymphocytes,Regulatory/chemistry/transplantation
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