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The eggs of the parasitic trematode Schistosoma mansoni are powerful inducers of a T helper type 2 (Th2) immune response and immunoglobulin E (IgE) production. S. mansoni egg extract (SmEA) stimulates human basophils to rapidly release large amounts of interleukin (IL)-4, the key promoter of a Th2 response. Here we show purification and sequence of the IL-4-inducing principle of S. mansoni eggs (IPSE). Stimulation studies with human basophils using SmEA fractions and natural and recombinant IPSE as well as neutralization and immunodepletion studies using antibodies to recombinant IPSE demonstrate that IPSE is the bioactive principle in SmEA leading to activation of basophils and to expression of IL-4 and IL-13. Regarding the mechanism of action, blot analysis showed that IPSE is an IgE-binding factor, suggesting that it becomes effective via cross-linking receptor-bound IgE on basophils. Immunohistology revealed that IPSE is enriched in and secreted from the subshell area of the schistosome egg. We conclude from these data that IPSE may be an important parasite-derived component for skewing the immune response toward Th2.

We have recently shown that soluble extracts from Schistosoma mansoni eggs (SmEA) triggered basophils from nonsensitized donors to rapidly release interleukin (IL)-4. Assuming that this mechanism might play a role in vivo in biasing the immune response towards a Th2 phenotype, we determined basic properties of the IL-4-inducing activity contained in SmEA. Sensitivity to pepsin digestion indicated protein nature. Binding to and specific elution from Concanavalin A-sepharose suggested that this protein contains mannose residues, thus being a glycoprotein. The IL-4-inducing activity was stable for 30 min at room temperature towards shifting the pH between 3 and 10. When incubated at 100 degrees C, it was stable at pH 3, but less stable at neutral and alkaline pH. Electroelution from an SDS-PAGE gel indicated an apparent molecular weight of the IL-4-inducing activity between 31 and 66 kDa. Although binding to purified human immunoglobulin E (IgE) and activating basophils IgE-dependently, SmEA appears to activate basophils in a non-antigen-specific way, since the cells were purified from noninfected donors. Because the IL-4-inducing activity was found to be released from eggs, it could be an important factor in the environment of the eggs skewing the immune response towards the Th2 phenotype.