CD4+CD25+ Regulatory T Cells Suppress Mast Cell Degranulation and Allergic Responses through OX40-OX40L Interaction

T regulatory (Treg) cells play a role in the suppression of immune responses, thus serving to induce tolerance and control autoimmunity. Here, we explored whether Treg cells influence the immediate hypersensitivity response of mast cells (MCs). Treg cells directly inhibited the FcɛRI-dependent MC de...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2008-11, Vol.29 (5), p.771-781
Main Authors: Gri, Giorgia, Piconese, Silvia, Frossi, Barbara, Manfroi, Vanessa, Merluzzi, Sonia, Tripodo, Claudio, Viola, Antonella, Odom, Sandra, Rivera, Juan, Colombo, Mario P., Pucillo, Carlo E.
Format: Article
Language:English
Subjects:
Allergies
Animals
Calcium - metabolism
Cell Degranulation
Cell Line, Tumor
CELLIMMUNO
Cloning
Cytokines
Gene Knockdown Techniques
Histamine Release
Humans
Hypersensitivity - immunology
Hypersensitivity - metabolism
Mast Cells - cytology
Mast Cells - immunology
Mast Cells - metabolism
Membrane Glycoproteins - metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Phospholipase C gamma - metabolism
Receptors, OX40 - metabolism
Software
T-Lymphocytes, Regulatory - cytology
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
Tumor Necrosis Factors - metabolism
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Summary:T regulatory (Treg) cells play a role in the suppression of immune responses, thus serving to induce tolerance and control autoimmunity. Here, we explored whether Treg cells influence the immediate hypersensitivity response of mast cells (MCs). Treg cells directly inhibited the FcɛRI-dependent MC degranulation through cell-cell contact involving OX40-OX40L interactions between Treg cells and MCs, respectively. When activated in the presence of Treg cells, MCs showed increased cyclic adenosine monophosphate (cAMP) concentrations and reduced Ca2+ influx, independently of phospholipase C (PLC)-γ2 or Ca2+ release from intracellular stores. Antagonism of cAMP in MCs reversed the inhibitory effects of Treg cells, restoring normal Ca2+ responses and degranulation. Importantly, the in vivo depletion or inactivation of Treg cells caused enhancement of the anaphylactic response. The demonstrated crosstalk between Treg cells and MCs defines a previously unrecognized mechanism controlling MC degranulation. Loss of this interaction may contribute to the severity of allergic responses.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2008.08.018