EARLY IL-4 PRODUCTION BY NON-CD4(-HELPER-2 CELL RESPONSE TO SCHISTOSOMA-MANSONI EGGS() CELLS AT THE SITE OF ANTIGEN DEPOSITION PREDICTS THEDEVELOPMENT OF A T)

Cytokines play a major role in promoting naive Th cells to differentia te into Th1 or Th2 cells. While IL-4 is recognized as the primary pro- Th2 inducing cytokine, the identity of its cellular sources during the development of a Th2 response remains unclear. We have used Schistoso ma mansoni eggs, potent stimulators of Th2 responses both during the n atural progression of murine schistosomiasis and when experimentally i solated and injected into normal mice, to examine IL-4 production earl y in the evolution of an Ag-driven Th2 response. Analysis of peritonea l exudate cells by IL-4 specific reverse transcriptase-PCR and ELISPOT , at times following i.p. egg injection in naive C57BL/6 mice, reveale d a marked, transient elevation in IL-4 production at 2 to 12 h after Ag exposure. This response was temporally accompanied by eosinophil an d neutrophil infiltration and mast cell disappearance. The pattern of early IL-4 production and peritoneal cell infiltration was observed in egg-injected CD4(+) cell-depleted and nude C57BL/6 mice, strongly sug gesting that a non-T cell is the source of early IL-4 and that the sti mulus leading to the egg-induced changes in cellular composition are T cell independent. In addition to IL-4 transcripts, peritoneal exudate cells from egg-injected T cell replete or deficient mice contained IF N-gamma and IL-12 transcripts. Control i.p. PBS injections led to no o r minimal cytokine gene transcription. Early IL-4 was predictive of su bsequent Th2 response development since, in contrast to C57BL/6 mice, egg-injected BALB/c mice demonstrated no detectable IL-4 production at 12 h and mounted a comparatively weak egg Ag-specific Th2 response.