Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses

T1/ST2 is an orphan receptor of unknown function that is expressed on the s urface of murine T helper cell type 2 (Th2), but not Th1 effector cells. In vitro blockade of T1/ST2 signaling with an immunoglobulin (Ig) fusion prot ein suppresses both differentiation to and activation of Th2, but not Th1 e ffector populations. In a nascent Th2-dominated response, anti-T1/ST2 monoc lonal antibody (mAb) inhibited eosinophil infiltration, interleukin 5 secre tion, and IgE production. To determine if these effects were mediated by a direct effect on Th2 cells, we next used a murine adoptive transfer model o f Th1- and Th2-mediated lung mucosal immune responses. Administration of ei ther T1/ST2 mAb or T1/ST2-Ig abrogated Th2 cytokine production in vivo and the induction of an eosinophilic inflammatory response, but failed to modif y Th1-mediated inflammation. Taken together, our data demonstrate an import ant role of T1/ST2 in Th2-mediated inflammatory responses and suggest that T1/ST2 may prove to be a novel target for the selective suppression of Th2 immune responses.