The Schistosoma mansoni egg-derived r38 peptide-induced Th1 response affects the synchronous pulmonary but not the asynchronous hepatic granuloma growth

The p38 peptide derived from Schistosoma mansoni egg-antigens (SEA) is a pr eferential inducer of the Th1 response. In the present study, we investigat ed whether induction of a p38-specific Th1 or Th2 response can influence gr anuloma development in infected or sensitized mice. Mice sensitized with SE A/IL-12 3 weeks after infection but before worm oviposition commenced devel oped Th1 cytokine responses and had significantly reduced hepatic granuloma size. Similar immunization with p38/IL-12 induced a strong peptide-specifi c Th1, mixed SEA-specific Th1/Th2 responses without effect on hepa tic gran uloma development. Presentation of p38 with alum or alum/IL-12 mixture enha nced Th2 cytokine responses and hepatic granuloma sizes. in the synchronize d pulmonary model, sensitization of naive mice with p38/IL-12 induced a str ong Th1 cytokine production to p38 and SEA, led to a moderate increase in g ranuloma growth at days 4 and 8 following egg injection and actually promot ed the resolution of the lesion by day 16. Sensitization with p38 in alum i nduced Th2 cytokine production and generated the largest granulomas whereas the p38/alum/IL-12 sensitized group showed intermediate results in cytokin e production and granuloma growth. Thus, in infected mice, the p38 induced strong Th1 response was insufficient to cross-regulate the evolving Th2 env ironment that generated large granulomas.