Khurram Qadir

Th2-type granuloma development in acute murine schistosomiasis is only partly dependent on CD4+ T cells as the source of IL-4

Schistosome granulomas produce IL‐4, important for Th2 granuloma expression. We defined the origins of IL‐4 within these granulomas and the role of IL‐4‐producing CD4+ T cells in Th2 granuloma development. Dispersed granuloma cells spontaneously produced IL‐4 independently of T cells, whereas IL‐5 production was T cell dependent. Granuloma IL‐4 mRNA localized to the non‐T cells and IL‐5 to T cells. Granuloma CD4+ T and NK cells, but not B cells produced IL‐4 and IL‐5 in vitro. B cell–/– mice generated Th2 granulomas that produced IL‐4 and IL‐5 normally. Granuloma eosinophils expressed no IL‐4 or IL‐5 mRNA. Granulomas in WWv mast cell‐deficient mice lacked mast cells. The dispersed granuloma cells from WWv mice released IL‐4 only after T cell stimulation, suggesting that mast cells influenced the constitutive component of IL‐4 production. Rag‐1 animals (T/B/NK T cell deficient) given schistosomiasis after reconstitution with splenocytes from naive mice produced Th2 granulomas. Mice reconstituted to create selective CD4+ T cell IL‐4 knockout animals developed eosinophilic granulomas that made IL‐4. Thus, granulomas contain several cell types that produce IL‐4. Mast cells are not needed to form Th2 granulomas, but influence IL‐4 release. Th2 granuloma development in schistosomiasis is only partly dependent on IL‐4‐producing CD4+ T cells.