Gri Giorgia, Piconese Silvia, Frossi Barbara, Manfroi Vanessa, Merluzzi Sonia, Tripodo Claudio, Viola Antonella, Odom Sandra, Rivera Juan, Colombo Mario P, Pucillo Carlo E
Department of Biomedical Science and Technology, University of Udine, 33100 Udine, Italy.
Immunity. 2008 Nov 14;29(5):771-81. doi: 10.1016/j.immuni.2008.08.018.
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.
调节性T（Treg）细胞在抑制免疫反应中发挥作用，从而有助于诱导免疫耐受并控制自身免疫。在此，我们探究了Treg细胞是否影响肥大细胞（MC）的速发型超敏反应。Treg细胞通过细胞间接触直接抑制FcεRI依赖的MC脱颗粒，这种接触分别涉及Treg细胞与MC之间的OX40-OX40L相互作用。当在Treg细胞存在的情况下被激活时，MC显示出环磷酸腺苷（cAMP）浓度增加且Ca²⁺内流减少，这与磷脂酶C（PLC）-γ2或细胞内储存的Ca²⁺释放无关。MC中cAMP的拮抗作用逆转了Treg细胞的抑制作用，恢复了正常的Ca²⁺反应和脱颗粒。重要的是，Treg细胞的体内耗竭或失活导致过敏反应增强。Treg细胞与MC之间已证实的相互作用定义了一种以前未被认识的控制MC脱颗粒的机制。这种相互作用的丧失可能导致过敏反应的严重程度增加。
