T1/ST2-deficient mice demonstrate the importance of T1/ST2 in developing primary T helper cell type 2 responses

We have generated mice with a deficiency in T1/ST2 expression to clarify th e roles of T1/ST2 in T helper cell type 2 (Th2) responses. Using immunologi cal challenges normally characterized by a Th2-like response, we have compa red the responses of T1/ST2-deficient mice with those generated by wild-typ e mice. Using a primary pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that granuloma formation, characterized by eo sinophil infiltration, is abrogated in T1/ST2-deficient mice. Furthermore, we clearly demonstrate that in the absence of T1/ST2 expression, the levels of Th2 cytokine production are severely impaired after immunization. Thus, in a secondary pulmonary granuloma model, draining lymph node cells from t he T1/ST2-deficient animals produced significantly reduced levels of IL-4 a nd IL-5, despite developing granulomas of a magnitude similar to those of w ild-type mice and comparable antigen-specific immunoglobulin isotype produc tion. These data clearly demonstrate that T1/ST2 expression plays a role in the development of Th2-Like cytokine responses and indicate that effector functions are inhibited in its absence.