Polarization of the immune response to the single immunodominant epitope of p38, a major Schistosoma mansoni egg antigen, generates Th1- or Th2-type cytokines and granulomas

Abstract

In schistosomiasis mansoni, helminth eggs secrete soluble egg antigens (SEA) that induce T-cell-mediated granulomatous tissue responses. The cloned 38-kDa peptide (p38) of SEA was shown to induce and elicit Th1-type responsiveness in 1t-2k mice. Subsequently, the immunodominant T-cell epitope (P4) of p38 was shown to elicit pulmonary granuloma formation and Th1-type cytokine production in sensitized or infected mice. Here, we report that the immune response to p38 or P4 can be polarized to a Th1 or Th2 profile when the peptides are presented intraperitoneally in soluble recombinant interleukin-12 (IL-12) or alum adjuvant, respectively. The Th1 or Th2 profile was verified by cytokine secretion, enzyme-linked spot assay, and antibody isotype characterization. Importantly, the polarized immune response generated two types of pulmonary granulomas around injected P4-coated beads. The type 1 granulomas were smaller and contained mononuclear cells and occasional thin strands of deposited collagen. In contrast, the type 2 lesions were larger and contained mononuclear cells, large numbers of eosinophils, and several thick bands of deposited collagen. By reverse transcription-PCR cytokine, message in the type 1 granuloma-bearing lungs was found for gamma interferon, tumor necrosis factor alpha, and inducible nitric oxide synthase but not for IL-4 or IL-5. Conversely, lungs with type 2 granulomas had message only for IL-4 and IL-5. These results show that in the proper cytokine environment, the response to a strong Th1 inducer peptide can be deviated to a Th2 profile.