SCHISTOSOMA-MANSONI EGG-INDUCED EARLY IL-4 PRODUCTION IS DEPENDENT UPON IL-5 AND EOSINOPHILS

The initial immune response to Schistosoma mansoni eggs presumably res ults in IL-4 production, as schistosome eggs are strong Th2-inducing a ntigens and the differentiation of antigen-specific Th2 cells is large ly dependent on the presence of IL-4 during priming of naive Th cells. Consistent with this concept, intraperitoneal injection of mice with schistosome eggs results in an upregulation of IL-4 production by peri toneal exudate cells (PECs) within 12 h. Egg-induced IL-4 is rapidly b ound by its receptor, suggesting that this cytokine is utilized by a c ell type present at the site of antigen deposition or is complexed to soluble receptor. The peak of early IL-4 production is accompanied by a local eosinophilia and the apparent disappearance of mast cells. Stu dies utilizing either IL-4, IL-5, or mast cell-deficient mice indicate that the eosinophilia is dependent on mast cells and IL-5 and indepen dent of IL-4. Strikingly, egg-induced IL-4 production is absent in ani mals lacking the early peritoneal eosinophilia. Immunocytochemical ana lysis of PEC following egg injection indicates that the eosinophils th emselves make IL-4. These data strongly suggest that egg-induced IL-5 plays an essential role in recruiting eosinophils to the site of antig en deposition and that it is these eosinophils that then directly prod uce early IL-4.