Adoptive transfer of Treg cells counters adverse effects of Toxoplasma gondii infection on pregnancy

Abstract

Acute infection with Toxoplasma gondii (T. gondii) during pregnancy is associated with adverse outcomes. The mechanisms that cause this phenomenon are not clear. Regulatory T cells (Tregs) are involved in maternal tolerance, and here we observed a decrease in the absolute numbers of CTLA-4(+) Tregs and PD-1(+) Tregs in spleen and at the fetal-maternal interface in T. gondii-infected mice. Our results suggest that T. gondii induces apoptosis of Tregs. Additionally, we found that the expression of CTLA-4 and PD-1 on Tregs at fetal-maternal interface were higher than on spleen cells from normal pregnant mice. Therefore, we adoptively transferred Tregs from fetal-maternal interface or from spleens of normal pregnant mice into infected pregnant mice. Pregnancy outcomes were improved when Tregs were transferred from the fetal-maternal interface but not from the spleen. The mechanism appears to be through up-regulation of the number of CTLA-4(+) Tregs and PD-1(+) Tregs and correction of the imbalance between tolerant cytokines (IL-10, TGF-β) and inflammatory cytokines (IFN-γ). Our data indicate that Tregs at fetal-maternal interface express high levels of inhibitory molecules that play a vital immuno-protective role during pregnancy.

Keywords: CD4+ Foxp3+ regulatory T cell; Toxoplasma gondii; adoptive transfer; pregnancy.