It has been known that Schistosoma infections induce immunoregulatory pathways as a survival mechanism. Regulatory CD4+ T lymphocytes (T reg) are the main cells that participate in this response. We aim of this study was to evaluate the regulatory signature mediated by T reg lymphocytes from individuals infected with S. mansoni. MATERIALS AND METHODS: Of the 19 participants, 12 (63,1%) had S. mansoni infection and 7 (36,8%) had no infection. Regulatory lymphocytes were obtained from PBMC and stimulated with the S. mansoni egg antigen (SEA) to phenotypic and intracellular cytokine evaluation performed by flow cytometry. T reg cells were then isolated with magnetic beads for use in T reg lymphocyte-depleted cultures. In these cultures, the levels of IL-10, IL-13, Il-17 and IFN-γ were evaluated by ELISA. RESULTS: We observed higher frequencies of Treg lymphocytes (TCD4+CD25+FoxP3+), as well as higher expression of IL-10 and TGF-β by these cells. It was also observed in infected individuals a higher frequency of CD4+CD25+FoxP3+PD-1+ T cells, while there was no difference in the expression of CTLA-4 by these lymphocytes. Increased PD-1 and TGF-β expression were also observed in non-regulatory T lymphocyte populations (CD4+CD25LowFOXP3neg). Individuals infected with S. mansoni have higher levels of IL-10 and IL-13 in the PBMC supernatant cultures and lower levels of IFN-g compared to non-infected individuals. T reg cell depletion led to a reduction of IL-10 and IL-13 levels, whereas it did not alter IFN-g levels in the group of infected individuals. CONCLUSION: In individuals infected with S. mansoni the regulatory mechanisms seem to involve IL-10, TGF-β, and PD-1 pathways, but not CTLA-4. Additionally, the expression of TGF-β, PD-1, is not restricted to regulatory populations. These data contribute to increase our knowledge of pathways explored by these parasites favoring the survival of S. mansoni.