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

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• 作者：Giorgia Gri ; Silvia Piconese ; Barbara Frossi ; Vanessa Manfroi ; Sonia Merluzzi ; Claudio Tripodo ; Antonella Viola ; S ; ra Odom ; Juan Rivera ; Mario P. Colombo ; Carlo E. Pucillo
• 刊名：Immunity
• 出版年：2008
• 出版时间：14 November 2008
• 年：2008
• 卷：29
• 期：5
• 页码：771-781
• 全文大小：775 K

文摘

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 FcRI-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.