Interleukin-4 Receptor α Chain and STAT6 Signaling Inhibit Gamma Interferon but Not Th2 Cytokine Expression within Schistosome Granulomas

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Abstract
Compared to wild-type (WT) mice, schistosome granulomas in Stat6 knockout (KO) mice lacked eosinophils and had Th1 features. Interleukin-4 (IL-4) acts through Stat6 in assisting Th2 cell development. The importance of Stat6 for Th2-cell development within schistosome granulomas had not been explored. Therefore we studied gamma interferon (IFN-γ), IL-4, and IL-5 production in granulomas from Stat6 KO and WT mice. Dispersed granuloma cells from Stat6 KO and WT mice made similar amounts of IL-4 and IL-5. Only Stat6 KO granuloma cells released IFN-γ. Granuloma T cells contained most of the IL-4, IL-5, and IFN-γ mRNA and secreted these cytokines. In Stat6 KO mice, 16.6% of the granuloma cells were CD4+. Of these, 10.7% stained for IFN-γ and/or IL-4 by intracytoplasmic flow analysis. Few CD4− T cells stained positively. The IL-4-producing T cells did not stain for DX5 or with labeled α-GalCer CD1d tetramer, suggesting an absence of NK T cells. Thus, conventional Th cells in Stat6 KO granulomas produce IFN-γ and Th2 cytokines. Stat6 limits IFN-γ production but is unnecessary for Th2-cell development or localization within the granuloma.