title: 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.
authors.affiliation: Department of Immunology, Binzhou Medical University, Yantai.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Radiology, Affiliated Hospital of Binzhou Medical University, Shandong, China.
authors.forename: Mingdong
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Immunology, Binzhou Medical University, Yantai.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Immunology, Binzhou Medical University, Yantai.
authors.forename: Xianbing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Immunology, Binzhou Medical University, Yantai.
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Binzhou Medical University, Yantai.
authors.forename: Yuzhu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Immunology, Binzhou Medical University, Yantai.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Binzhou Medical University, Yantai.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Hu
mesh_terms: D000818:Animals; D016207:Cytokines / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D016219:Immunotherapy, Adoptive / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology / Q000469:parasitology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D014122:Toxoplasma / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology / Q000628:therapy*
chemical_list: D016207:Cytokines
keywords: CD4+ Foxp3+ regulatory T cell; Toxoplasma gondii; adoptive transfer; pregnancy