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IL-33, an IL-1 family member and ligand for the IL-1 receptor-related protein ST2, has been associated with induction of Th2 cytokines such as IL-4, IL-5, and IL-13. Here, we report that IL-33 can initiate IL-9 protein secretion in vitro in human CD4+ T cells and basophils isolated from peripheral blood. TGF-&bgr; has been described as a critical factor for IL-9 induction in Th2 cells; however, we found that TGF-&bgr; also induces co-production of IL-9 in purified, naïve (>99%) CD4+CD45RA+CD45RO- CD25- T cells differentiated towards a Th1 profile. Subsequently, it was demonstrated that TGF-&bgr; is important, although not an absolute requirement, for IL-9 production in CD4+ T cells. IL-9 production by purified (>95%) human basophils, cultured for 24 h with IL-3 or IL-33, was found, with a strong synergy between the two, likely to be explained by the IL-3 upregulated ST2 expression. Collectively, these data indicate that barrier functioning cells are important for the regulation of IL-9 production by immune cells in inflamed tissue. [ABSTRACT FROM AUTHOR]