Characterization and regulation of TH1/TH2 type cytokine responses to a major Schistosoma mansoni egg antigen (P38)

In murine schistosomiasis mansoni, Th cell responses to soluble egg antigens (SEA) mediate inflammatory granuloma formation around deposited eggs and subsequent fibrosis. Previously, a peptide component of SEA, designated as p38 or p40, was cloned and demonstrated to be a potent immunogen that preferentially induces a Th1 type response. In this study, the immunodominant T cell epitope of p38 was localized within the peptide P4, with sequence KSDNQIKAVPASQAL. Immunization experiments with p38 in various adjuvants established that p38 could induce either Th1 or Th2 type cytokine responses directed to P4 peptide. The induced Th1 or Th2 cells mediated two types of granulomatous responses against P4-coated beads, manifested by different lesion size and cellular composition. This implies an important role of the priming environment in deciding the nature of the induced immunelinflammatory response. Upon exposure to eggs by immunization or during infection, the Th1 cell response to p38/P4 was induced immediately but rapidly diminished by the time the Th2 cytokine response to other egg antigens became dominant. The p38/P4-reactive Th1 cells participated in the incipient stage but might not be involved in florid granuloma formation. Conversely, the rising antibody production to p38 sustained throughout the chronic stage of the infection. While the induction of Th2 cell response to p38/P4 exacerbated the egg-induced granulomatous response, the induction of Th I cell response accelerated the development and resolution of pulmonary egg granulomas. This interesting observation could not be duplicated in infected mice where the induced Th1 type anti-p38 response was ineffective in the downregulation of the Th2 cell response to other egg antigens and associated granuloma formation. Thus the Th1, Th2 cell interaction and antagonism clearly play an important role in the development and resolution of the schistosome egg-induced granulomatous inflammation. The utility of p38/P4 peptides as potential antigens in attempts to modify and attenuate the course and pathology of granulomatous schistosomiasis in humans merits extensive field exploration.