Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases

Sasaki, Yasushi

doi:10.1093/molehr/gah044

Cited by 653 publications

(595 citation statements)

References 25 publications

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“…In humans, three independent studies have described both the systemic and decidual expansion of CD4 ϩ CD25 ϩ FOXP3 ϩ Treg populations in the first two trimesters of pregnancy (14 -16). Also, the proportion of Tregs is reported to be much lower in deciduas of women with RSA (15). In the present study we demonstrate that women with RSA had similar Treg frequencies in the CD4 ϩ population at both the late follicular and luteal phases of the menstrual cycle.…”

Section: Discussionsupporting

confidence: 66%

“…In both mice and humans it has been reported that an expansion of Treg cells is necessary to mediate maternal tolerance to the fetus (13)(14)(15)(16). It was thus of interest to investigate the normal behavior of Tregs during the menstrual cycle of women who had 3 or more recurrent spontaneous abortions.…”

Section: Decreased Treg Frequencies In Women With Rsa Compared With Fmentioning

confidence: 99%

“…Supporting their role in response to viral infections, Treg numbers are higher in patients who progressed to the chronic phase of hepatitis C virus infection (12). However, apart from situations where there is almost total absence of these cells, some of the most crucial evidence for their participation in maintaining tolerance is their role in mediating maternal tolerance of the fetus (13)(14)(15)(16).…”

mentioning

confidence: 99%

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Expansion of CD4+CD25+and FOXP3+ Regulatory T Cells during the Follicular Phase of the Menstrual Cycle: Implications for Human Reproduction

Arruvito¹,

Sanz²,

Banham

et al. 2007

The Journal of Immunology

385

325

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Regulatory T cells (Tregs) are thought to affect the severity of various infectious and autoimmune diseases. The incidence of autoimmune disease is higher in fertile women than in men. Thus, we investigated whether Treg numbers were modulated during the menstrual cycle by sex hormones. In fertile nonpregnant women, we detected an expansion of CD4+CD25+FOXP3+ Tregs in the late follicular phase of the menstrual cycle. This increase was tightly correlated with serum levels of estradiol and was followed by a dramatic decrease in Treg numbers at the luteal phase. Women who have had recurrent spontaneous abortions (RSA) showed similarly low numbers of Tregs at both the follicular and luteal phases, comparable to numbers we observed in postmenopausal women. In addition to decreased numbers, Tregs from women with RSA were also functionally deficient, as higher numbers were required to exert a similar magnitude of suppression to CD4+CD25+FOXP3+ cells from fertile women. Consequently, reproductive failure might result from the inability of Tregs in women with RSA to expand during the preimplantatory phase combined with their lower functional capacity. Additionally, the modulation of Treg numbers we observed in fertile women suggests that the stage of the menstrual cycle should be taken into account when Treg numbers are investigated clinically.

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Section: Discussionsupporting

confidence: 66%

Section: Decreased Treg Frequencies In Women With Rsa Compared With Fmentioning

confidence: 99%

mentioning

confidence: 99%

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Expansion of CD4+CD25+and FOXP3+ Regulatory T Cells during the Follicular Phase of the Menstrual Cycle: Implications for Human Reproduction

Arruvito¹,

Sanz²,

Banham

et al. 2007

The Journal of Immunology

385

325

View full text Add to dashboard Cite

show abstract

“…Abortion-prone mice showed a diminished Treg activity and fetal rejection could be completely prevented by adoptive transfer of Treg exclusively from normal pregnant mice [28]. Recent data suggest that similar mechanisms should exist in humans [30].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, fetal rejection could be completely prevented by adoptive transfer of Treg exclusively from normal pregnant mice [28]. Other authors confirmed the important role of Treg in human pregnancy [29,30].…”

Section: Introductionmentioning

confidence: 93%

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

et al. 2005

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The mechanisms underlying immune tolerance during pregnancy are poorly understood. In this regard, Treg seem to play an important role in mediating maternal tolerance to the fetus. We proposed a crucial role of T regulatory cells (Treg) in avoiding immunological rejection of the fetus after observing diminished number and function of Treg in abortion-prone mice. We further confirmed the protective role of Treg during pregnancy by transferring pregnancy-induced Treg into abortion-prone mice, which prevented rejection. Here, we analyzed the mechanisms involved in Treg-mediated protection. As expected, Treg therapy prevented abortion, while expanding the peripheral and thymic Treg population. Surprisingly, the decidual levels of the Th1 cytokines IFN-c and TNF-a were not diminished after therapy. Interestingly, the mRNA levels of leukemia inhibitory factor, TGF-b and heme oxygenase-1 at the fetal-maternal interface were dramatically up-regulated after Treg transfer, while the levels of indolamine 2,3-dioxygenase remained unchanged. Our data suggest that Treg treatment can not prevent T cell infiltration or high Th1 levels but is able to create a privileged tolerant microenvironment at the fetal-maternal interface, further shedding light onto the molecular mechanisms involved in pregnancy tolerance.

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Allogeneic murine pregnancy models for assessing the developmental effects of immune‐stimulating antibodies: Challenges in reproducibility

Thompson

Danberry

Bunch

et al. 2019

Birth Defects Research

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Literature suggests that murine allogeneic pregnancy models are an alternative approach for evaluating the developmental toxicity of immune-stimulating agents. In this study, multiple syngeneic and allogeneic murine pregnancy models were used to assess the potential embryo-fetal effects of four different murine antibodies (IgG 1 or IgG 2 ) that activate the immune system by binding to T-cell receptors (PD-L1, LAG-3, and GITR).The pregnancy models were generated by within and between matings of five different inbred strains of mice (CBA/CaJ, DBA/2J, BALB/c, C57BL/6, and CBA/J). The antibodies were administered every 2-3 days by intraperitoneal injection (n = 12-29/group) during gestation days 6 to 14. There were no differences in embryo-fetal endpoints between the allogeneic and syngeneic pregnancies. Additionally, treatment with the antibodies had no effect on mean postimplantation loss in either the syngeneic or allogeneic pregnancies despite confirmation of pharmacologically-relevant systemic exposures.These results suggest that allogeneic murine pregnancy models need further validation and testing before they can be reliably used as an alternative approach for assessing the developmental effects of agents that stimulate the immune system. K E Y W O R D S allogeneic pregnancy, developmental effects, immune stimulation, maternofetal tolerance, monoclonal antibodies, T-cells

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Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases

Cited by 653 publications

References 25 publications

Expansion of CD4+CD25+and FOXP3+ Regulatory T Cells during the Follicular Phase of the Menstrual Cycle: Implications for Human Reproduction

Expansion of CD4+CD25+and FOXP3+ Regulatory T Cells during the Follicular Phase of the Menstrual Cycle: Implications for Human Reproduction

Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

Allogeneic murine pregnancy models for assessing the developmental effects of immune‐stimulating antibodies: Challenges in reproducibility

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