Role for CTLA-4 but not CD25(+) T cells during Schistosoma mansoni infection of mice

Schistosoma mansoni infection of mice increases the frequency of cells that are CD4(+)CD25(+) in the acute (4 and 8 weeks) and chronic (16 week) stages of infection. Depletion of > 85% of CD25(+) cells in the acute or chronic stages of schistosome infection caused no overt changes in morbidity or immunological responses. The absence of effect in mice with CD25(+) cells depleted may be due to the preferential expression of IL-4 and IL-10, two cytokines that are protective in schistosome infection, on CD25(-) CD4(+) cells. We also assessed infection-induced changes of other regulatory markers, GITR, CD103 and CTLA-4 on CD4(+) cells. We identified a marked expansion of CTLA-4(+) population on CD25(-) CD4(+) cells in acute and chronic infection. Blocking of CTLA-4 during acute, but not chronic infection, caused significant weight loss and altered the type 2 cytokine response of mice, with increased IL-4 and IL-5 production associated with significantly more Th2 cells and eosinophils in the liver granuloma. This study illustrates the complexity of regulation of T cells in schistosome infection and highlights a specific role for CTLA-4(+), but not CD25(+) cells, in the regulation of Th2 responses in helminth infection.