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

Abstract

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.

T cells in helminth infection: the regulators and the regulated

“…For example, in Trichuris muris infection, early intervention with anti-GITR, but not anti-CD25, antibodies is most effective at reducing worm loads [31]. Anti-CD25 depletion is reported to be ineffective at boosting immunity to other helminths, including Schistosoma mansoni [32,33] and Trichinella spiralis [34]. Experiments with Foxp3-DTR mice will be interesting in this regard and, although Foxp3-depleted mice are not more resistant Box 1.…”

“…33,No. 4 to the gastrointestinal nematode Heligmosomoides polygyrus in the first 14 days of infection [19], a longer time may be required for primary protective Th2 immunity to take effect in this infection.…”

Blockade of B7-H1 (Programmed Death Ligand 1) Enhances Humoral Immunity by Positively Regulating the Generation of T Follicular Helper Cells

“…All helminth infections, immunology, parasitology, and pathology were as described (15,16). S. mansoni eggs were isolated and soluble egg Ag (SEA) was prepared as described (15).…”

CTLA-4 and CD4+CD25+ Regulatory T Cells Inhibit Protective Immunity to Filarial Parasites In Vivo

“…ϩ Treg cells (34,35,47). Although neutralizing CTLA-4 alone during an established L. sigmodontis infection did not promote protective immunity, when CTLA-4 neutralization was performed in combination with depletion of CD25…”