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* Department of Biology, Virginia Commonwealth University, Richmond, VA 23284;
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases and
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
Mast cell activation is associated with atopic and inflammatory diseases, but the natural controls of mast cell homeostasis are poorly understood. We hypothesized that CD4+CD25+ regulatory T cells (Treg) could function in mast cell homeostasis. In this study, we demonstrate that mast cells can recruit both Treg and conventional CD4+ T cells (Tconv). Furthermore, Treg, but not Tconv, suppress mast cell Fc
RI expression. Despite the known inhibitory functions of IL-10 and TGFβ1, FcRI suppression was independent of IL-10 and TGF-β1 and required cell contact. Surprisingly, coculture with either Treg or Tconv cells suppressed IgE-mediated leukotriene C4 production but enhanced cytokine production by mast cells. This was accompanied by a selective increase in FcRI-mediated Stat5 phosphorylation, which is a critical mediator of IgE-mediated cytokine secretion. These data are the first direct demonstration that mast cells can recruit Treg and illustrate that T cell interactions can alter the mast cell response.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by grants to the Ryan Laboratory from the National Institutes of Health (1R01 AI059638 and 1R01 CA91839) and the Jeffress Trust Foundation (J-833).
2 Address correspondence and reprint requests to Dr. John J. Ryan, Virginia Commonwealth University, Biology Department, Box 842012, Richmond, VA 23284-2012. E-mail address: jjryan{at}saturn.vcu.edu
3 Abbreviations used in this paper: Treg, regulatory T cell; BMMC, bone marrow-derived mast cell; DNP, 2,4-dinitrophenyl; HA, hemagglutinin; Tconv, conventional CD4+CD25– T cell.
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