Schistosoma mansoni Triose Phosphate Isomerase Peptide MAP4 is Able to Trigger Naı¨ve Donor Immune Response Towards a Type-1 Cytokine Profile

Abstract

We evaluated the ability of naïve monocyte-derived dendritic cells (DC) to sensitize autologous peripheral blood mononuclear cells (PBMC) to the schistosome vaccine candidate MAP4 using a priming in vitro (PIV) assay. MAP4 is a multiple antigen peptide containing B- and T-cell epitopes derived from the glycolytic enzyme triose phosphate isomerase. PBMC primed and restimulated with MAP4 first and secondary recalls (MAP4 PIV cells) were examined for cell phenotype and cytokine production. We found that after the first recall stimulation with MAP4, the major cell population was predominantly CD4+ T-cell subsets (68.5%), CD8+high (16%) and CD19+ (10%). Additionally, MAP4 PIV cells significantly expressed CD4+-HLA-DR+, -CD54+, -CD45RO+ (P < 0.0001) and -CD25+ (P < 0.0004) together with significant expression of CD80+ on CD19+ B cells (P < 0.007). Cytokine production from activated MAP4 PIV cells was predominantly Th1-like, consisting mainly of IFN-γ. Interestingly, IFN-γ production was suppressed when Schistosoma mansoni-soluble egg antigen (SEA) was added to a MAP4 PIV cell culture. Furthermore, addition of MAP4 to a SEA PIV cell culture significantly reduced secretion of IL-10. The present findings add to the knowledge gained from studies in the mouse model, and our results show that naïve donor DC, sensitized with MAP4, were able to prime and clonally expand MAP4-specific T cells towards a Th1-type response.