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J Allergy Clin Immunol. 2009 Jun;123(6):1287-96.e2. doi: 10.1016/j.jaci.2009.03.022. Epub 2009 May 8.

CD4+CD25+ regulatory T cells suppress contact hypersensitivity reactions through a CD39, adenosine-dependent mechanism.

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  • 1Department of Dermatology, University Hospital Heidelberg, Heidelberg, Germany.

Abstract

BACKGROUND:

Injection of regulatory T (Treg) cells into sensitized mice abrogates the elicitation phase of contact hypersensitivity (CHS) reactions by blocking the adherence of leukocytes to vascular endothelium.

OBJECTIVE:

We set out to analyze whether adenosine, a suppressive factor recently described as produced by Treg cells, can account for the suppression of the effector T-cell-endothelial cell (EC) interaction.

METHODS:

T cells and ECs were cultured in the presence of adenosine, and expression of adhesion molecules and adhesion of T cells to ECs under shear stress were assessed. Furthermore, we injected Treg cells derived from ectonucleotidase-deficient (CD39-/-) mice into sensitized mice and analyzed the sticking and rolling of leukocytes during a CHS response using intravital microscopy.

RESULTS:

Adenosine or Treg cells, respectively, abrogated the adherence of effector T cells to ECs in vitro. Likewise, injection of adenosine and Treg cells abrogated the ear-swelling reaction, indicating a role of adenosine during Treg cell-induced suppression of CHS responses. As a source for Treg cell-derived adenosine, we identified the ectonucleotidase CD39 because CD39-deficient Treg cells did not prevent adhesion of leukocytes to the endothelium. Furthermore, we show that the impaired adhesion of effector T cells to inflamed endothelium was induced by adenosine-mediated downregulation of expression of E- and P-selectin on the vascular endothelium.

CONCLUSION:

Adenosine release by Treg cells is essential to block leukocyte adhesion to endothelium, providing a novel mechanism by which Treg cells mediate immune suppression in vivo.

PMID:
19427686
[PubMed - indexed for MEDLINE]
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