CD4+ CD25+ regulatory T cells suppress contact hypersensitivity reactions by blocking influx of effector T cells into inflamed tissue.
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.
Ring
Sabine
S
Department of Dermatology, University of Heidelberg, Heidelberg, Germany. Sabine.Ring@med.uni-hedelberg.de
Schäfer
Stephan C
SC
Mahnke
Karsten
K
Lehr
Hans-Anton
HA
Enk
Alexander H
AH
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D003877:Dermatitis, Contact / Q000276:immunology* / Q000517:prevention & control; D004848:Epithelium / Q000187:drug effects / Q000276:immunology; D006241:Haptens / Q000494:pharmacology; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000032:analysis / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D036904:Leukocyte Rolling / Q000276:immunology*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology* / Q000637:transplantation
D015704:CD4 Antigens; D006241:Haptens; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10