TY - JOUR
T1 - CD4+CD25+ Regulatory T Cells Suppress Mast Cell Degranulation and Allergic Responses through OX40-OX40L Interaction
AU - Gri, Giorgia
AU - Piconese, Silvia
AU - Frossi, Barbara
AU - Manfroi, Vanessa
AU - Merluzzi, Sonia
AU - Tripodo, Claudio
AU - Viola, Antonella
AU - Odom, Sandra
AU - Rivera, Juan
AU - Colombo, Mario P.
AU - Pucillo, Carlo E.
PY - 2008/11/14
Y1 - 2008/11/14
N2 - 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.
AB - 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.
KW - CELLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=55349084351&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55349084351&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2008.08.018
DO - 10.1016/j.immuni.2008.08.018
M3 - Article
C2 - 18993084
AN - SCOPUS:55349084351
VL - 29
SP - 771
EP - 781
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 5
ER -