Partial Regulatory T Cell Depletion Prior to Schistosomiasis Vaccination Does Not Enhance the Protection

CD4(+)CD25(+) regulatory T cells (Tregs) do not only influence self-antigen specific immune responses, but also dampen the protective effect induced by a number of vaccines. The impact of CD4(+)CD25(+) Tregs on vaccines against schistosomiasis, a neglected tropical disease that is a major public health concern, however, has not been examined. In this study, a DNA vaccine encoding a 26 kDa glutathione S-transferase of Schistosoma japonicum (pVAX1-Sj26GST) was constructed and its potential effects were evaluated by depleting CD25(+) cells prior to pVAX1-Sj26GST immunization. This work shows that removal of CD25(+) cells prior to immunization with the pVAX1-Sj26GST schistosomiasis DNA vaccine significantly increases the proliferation of splenocytes and IgG levels. However, CD25(+) cell-depleted mice immunized with pVAX1-Sj26GST show no improved protection against S. japonicum. Furthermore, depletion of CD25(+) cells causes an increase in both pro-inflammatory cytokines (e.g. IFN-γ, GM-CSF and IL-4) and an anti-inflammatory cytokine (e.g. IL-10), with CD4(+)CD25(-) T cells being one of the major sources of both IFN-γ and IL-10. These findings indicate that partial CD25(+) cell depletion fails to enhance the effectiveness of the schistosome vaccine, possibly due to IL-10 production by CD4(+)CD25(-) T cells, or other cell types, after CD25(+) cell depletion during vaccination.