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

J Infect Dis. 2014 Nov 1;210(9):1435-43. doi: 10.1093/infdis/jiu265. Epub 2014 May 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / analysis
  • Female
  • Flow Cytometry
  • Immunotherapy, Adoptive* / methods
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Placenta / chemistry
  • Pregnancy
  • Pregnancy Complications, Parasitic / immunology
  • Pregnancy Complications, Parasitic / parasitology
  • Pregnancy Complications, Parasitic / therapy*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / transplantation
  • Toxoplasma / immunology
  • Toxoplasmosis / immunology
  • Toxoplasmosis / therapy*


  • Cytokines