Ed Tregs may resist T. gondii ESA stimuli. Further studies are required to demonstrate the functional differences of Tregs from different stages of pregnancy. It was reported that the administration of anti-CD25 mAb at early pregnancy could induce implantation failure, while no effects were observed at late pregnancy [38]. However, anti-CD25 mAb may block not only Tregs, but also activated T lymphocytes [39]. In our study, to determine whether the diminished capacity of Tregs is causally associated with the fetal loss, we adoptively transferred CD4+CD25+ T cells isolated from the spleens of normal pregnant mice and pregnant mice injected with T. gondii ESA at G5 or at G15 and inject those cells into T. gondii ESAinjected pregnant mice at G5. Our data showed that the Tregs from the mice with T. gondii ESA injection at G15 ip reduced significantly the abortion rate, while the Tregs from the mice with T. gondii ESA injection at G5 ip failed to prevent the abortion. Apparently, these results demonstrated that the administration of T. gondii ESA did induce diminished capacity of CD4+CD25+ T cells at G5, and then Title Loaded From File resulted in the abortion. Although the adoptive transfering of Tregs failed to completely prevent abortion, it revealed that Tregs contributed partly, to the consequence. It is suggested that the different pregnancy outcomesT. gondii ESA Induced Tregs DysfunctionFigure 6. Apoptosis in local maternal-fetal tissues of pregnant mice with T. gondii ESA injection at G10. All data are presented as mean 6 SE, and analyzed by one-way ANOVA. (A)Top panel, cleaved Caspase-3 expression was analyzed by Western blot after the injection with T. gondii ESA and PBS at G10 or G15. Bottom panel, cleaved 1315463 Caspase-3 expression was quantified by densitometric analysis with Image J. (B) Top panel, Bcl-2 levels were analyzed by Western blot. Bottom panel, Bcl-2 expression was quantified by densitometric analysis with Image J. (C) Top panel, Bax levels were analyzed by Western blot. Bottom panel, Bax expression was quantified by densitometric analysis with Image J. (D) Bcl-2/Bax ratio. Statistical differences between groups are shown as follows: * p,0.05; *** p,0.001; # p.0.05. doi:10.1371/journal.pone.0069012.gof mice with the administration of T. gondii ESA at G5, G10 and G15 were due to the different effects of T. gondii ESA on the capacity of CD4+CD25+ T cells. Our data indicated that the administration of T. gondii ESA at early pregnancy could lead to the decreased number ofCD4+CD25+ T cells. Some studies demonstrated that CD4+CD25+ T cells can be regulated directly via triggering Toll-like receptor ligands [40], or indirectly via enhanced activation of APC or effector T cells [41]. In addition, enhanced apoptosis or a loss of function is also a causative event in regulatingT. gondii ESA Induced Tregs DysfunctionTreg cells [42,43,44]. Apoptosis of splenic CD4+ T cells during Toxoplasma infection has been observed by other researchers [45]. In a model of ocular toxoplasmosis, Title Loaded From File inflammatory cell apoptosis was implicated in disease pathogenesis [46]. T-cell apoptosis in the Peyer’s patches also accompanies intestinal necrosis during 23977191 oral T. gondii infection [47]. However, the susceptibility of CD4+CD25+ Tregs to apoptosis is controversial. Human CD4+CD25+ T cells are apoptosis-prone because of lower expression of the antiapoptotic molecule Bcl-2 than conventional lymphocytes [48]. On the other hand, murine CD4+CD25+ T cells are resistant to apoptosis induce.Ed Tregs may resist T. gondii ESA stimuli. Further studies are required to demonstrate the functional differences of Tregs from different stages of pregnancy. It was reported that the administration of anti-CD25 mAb at early pregnancy could induce implantation failure, while no effects were observed at late pregnancy [38]. However, anti-CD25 mAb may block not only Tregs, but also activated T lymphocytes [39]. In our study, to determine whether the diminished capacity of Tregs is causally associated with the fetal loss, we adoptively transferred CD4+CD25+ T cells isolated from the spleens of normal pregnant mice and pregnant mice injected with T. gondii ESA at G5 or at G15 and inject those cells into T. gondii ESAinjected pregnant mice at G5. Our data showed that the Tregs from the mice with T. gondii ESA injection at G15 ip reduced significantly the abortion rate, while the Tregs from the mice with T. gondii ESA injection at G5 ip failed to prevent the abortion. Apparently, these results demonstrated that the administration of T. gondii ESA did induce diminished capacity of CD4+CD25+ T cells at G5, and then resulted in the abortion. Although the adoptive transfering of Tregs failed to completely prevent abortion, it revealed that Tregs contributed partly, to the consequence. It is suggested that the different pregnancy outcomesT. gondii ESA Induced Tregs DysfunctionFigure 6. Apoptosis in local maternal-fetal tissues of pregnant mice with T. gondii ESA injection at G10. All data are presented as mean 6 SE, and analyzed by one-way ANOVA. (A)Top panel, cleaved Caspase-3 expression was analyzed by Western blot after the injection with T. gondii ESA and PBS at G10 or G15. Bottom panel, cleaved 1315463 Caspase-3 expression was quantified by densitometric analysis with Image J. (B) Top panel, Bcl-2 levels were analyzed by Western blot. Bottom panel, Bcl-2 expression was quantified by densitometric analysis with Image J. (C) Top panel, Bax levels were analyzed by Western blot. Bottom panel, Bax expression was quantified by densitometric analysis with Image J. (D) Bcl-2/Bax ratio. Statistical differences between groups are shown as follows: * p,0.05; *** p,0.001; # p.0.05. doi:10.1371/journal.pone.0069012.gof mice with the administration of T. gondii ESA at G5, G10 and G15 were due to the different effects of T. gondii ESA on the capacity of CD4+CD25+ T cells. Our data indicated that the administration of T. gondii ESA at early pregnancy could lead to the decreased number ofCD4+CD25+ T cells. Some studies demonstrated that CD4+CD25+ T cells can be regulated directly via triggering Toll-like receptor ligands [40], or indirectly via enhanced activation of APC or effector T cells [41]. In addition, enhanced apoptosis or a loss of function is also a causative event in regulatingT. gondii ESA Induced Tregs DysfunctionTreg cells [42,43,44]. Apoptosis of splenic CD4+ T cells during Toxoplasma infection has been observed by other researchers [45]. In a model of ocular toxoplasmosis, inflammatory cell apoptosis was implicated in disease pathogenesis [46]. T-cell apoptosis in the Peyer’s patches also accompanies intestinal necrosis during 23977191 oral T. gondii infection [47]. However, the susceptibility of CD4+CD25+ Tregs to apoptosis is controversial. Human CD4+CD25+ T cells are apoptosis-prone because of lower expression of the antiapoptotic molecule Bcl-2 than conventional lymphocytes [48]. On the other hand, murine CD4+CD25+ T cells are resistant to apoptosis induce.

Ed Tregs may resist T. gondii ESA stimuli. Further studies are

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