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

Giorgia Gri, Silvia Piconese, Barbara Frossi, Vanessa Manfroi, Sonia Merluzzi, Claudio Tripodo, Antonella Viola, Sandra Odom, Juan Rivera, Mario P. Colombo, Carlo E. Pucillo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)771-781
Number of pages11
JournalImmunity
Volume29
Issue number5
DOIs
Publication statusPublished - Nov 14 2008

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Keywords

  • CELLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Gri, G., Piconese, S., Frossi, B., Manfroi, V., Merluzzi, S., Tripodo, C., Viola, A., Odom, S., Rivera, J., Colombo, M. P., & Pucillo, C. E. (2008). CD4+CD25+ Regulatory T Cells Suppress Mast Cell Degranulation and Allergic Responses through OX40-OX40L Interaction. Immunity, 29(5), 771-781. https://doi.org/10.1016/j.immuni.2008.08.018