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RESEARCH PRODUCT
CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction.
Sandra OdomSilvia PiconeseBarbara FrossiMario P. ColomboSonia MerluzziJuan RiveraCarlo PucilloVanessa ManfroiAntonella ViolaGiorgia GriClaudio Tripodosubject
T-LymphocytesCELLIMMUNO; Animals; Calcium; Cell Line Tumor; Gene Knockdown Techniques; Histamine Release; Humans; Hypersensitivity; Mast Cells; Membrane Glycoproteins; Mice; Mice Inbred BALB C; Mice Inbred C57BL; Phospholipase C gamma; Receptors OX40; T-Lymphocytes Regulatory; Tumor Necrosis Factors; Cell Degranulation; Immunology and Allergy; Infectious Diseases; ImmunologyInbred C57BLmedicine.disease_causeHistamine ReleaseT-Lymphocytes RegulatoryCell DegranulationAutoimmunityMicechemistry.chemical_compoundReceptorsImmunology and AllergyOX40Mast CellsInbred BALB CMice Inbred BALB CTumorMembrane GlycoproteinsDegranulationhemic and immune systemsRegulatoryhumanitiesCell biologyTregInfectious DiseasesGene Knockdown TechniquesTumor Necrosis FactorsMembrane GlycoproteinMast cell; Treg; OX40-OX40L interactionIntracellularHumanCell DegranulationImmunologyInfectious Diseasechemical and pharmacologic phenomenaBiologybehavioral disciplines and activitiesArticleCell LineMast cellImmune systemCell Line TumorHypersensitivitymedicineAnimalsHumansCyclic adenosine monophosphatePhospholipase CAnimalPhospholipase C gammaReceptors OX40Mice Inbred C57BLchemistryCELLIMMUNOCell cultureGene Knockdown TechniqueImmunologyOX40-OX40L interactionCalciumTumor Necrosis Factordescription
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 FcεRI-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. © 2008 Elsevier Inc. All rights reserved.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2008-11-01 |