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PMID: 18993084 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction.

Immunity ·Vol. 29 ·No. 5 ·2008-11-14 ·Pages 771-81

Gri G, Piconese S, Frossi B, Manfroi V, Merluzzi S, Tripodo C, Viola A, Odom S, Rivera J, Colombo MP, Pucillo CE

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 FcvarepsilonRI-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 Ca(2+) influx, independently of phospholipase C (PLC)-gamma2 or Ca(2+) release from intracellular stores. Antagonism of cAMP in MCs reversed the inhibitory effects of Treg cells, restoring normal Ca(2+) 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.

MeSH Terms
Animals Calcium/metabolism Cell Degranulation Cell Line, Tumor Gene Knockdown Techniques Histamine Release Humans Hypersensitivity/immunology,metabolism Mast Cells/cytology,immunology,metabolism Membrane Glycoproteins/metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL OX40 Ligand Phospholipase C gamma/metabolism Receptors, OX40/metabolism T-Lymphocytes, Regulatory/cytology,immunology,metabolism Tumor Necrosis Factors/metabolism
Chemicals
Membrane Glycoproteins OX40 Ligand Receptors, OX40 Tnfrsf4 protein, mouse Tnfsf4 protein, mouse Tumor Necrosis Factors Phospholipase C gamma Calcium
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Gri Giorgia
Department of Biomedical Science and Technology, University of Udine, 33100 Udine, Italy.
Piconese Silvia
Frossi Barbara
Manfroi Vanessa
Merluzzi Sonia
Tripodo Claudio
Viola Antonella
Odom Sandra
Rivera Juan
Colombo Mario P
Pucillo Carlo E
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2008.08.018
Published
2008-11-14
Pages
771-81
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2590499
Subset
IM
Grants
Intramural NIH HHS · Z01 AR041156-01 · United States
Corrections
CommentIn
PMID: 22925181
External Links
PubMed source DOI: 10.1016/j.immuni.2008.08.018 PMC Full Text View journal details
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