Differentiation of ICOS+and ICOS−recent thymic emigrant regulatory T cells (RTE Tregs) during normal pregnancy, pre-eclampsia and HELLP syndrome

Regulatory T cells (Tregs) are indispensable for the control of immune homeostasis and have clinical potential as a cell therapy for treating autoimmunity. Tregs can lose expression of the lineage-defining Foxp3 transcription factor and acquire effector T cell (Teff) characteristics, a process referred to as Treg plasticity. The extent and reversibility of such plasticity during immune responses remain unknown. Here, using a murine genetic fate-mapping system, we show that Treg stability is maintained even during exposure to a complex microbial/antigenic environment. Furthermore, we demonstrate that the observed plasticity of Tregs after adoptive transfer into a lymphopenic environment is a property limited to only a subset of the Treg population, with the nonconverting majority of Tregs being resistant to plasticity upon secondary stability challenge. The unstable Treg fraction is a complex mixture of phenotypically distinct Tregs, enriched for naïve and neuropilin-1–negative Tregs, and includes peripherally induced Tregs and recent thymic emigrant Tregs. These results suggest that a “purging” process can be used to purify stable Tregs that are capable of robust fate retention, with potential implications for improving cell transfer therapy.

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Peripheral Dendritic Cells and CD4+CD25+Foxp3+ Regulatory T Cells in the First Trimester of Normal Pregnancy and in Women with Recurrent Miscarriage

PLoS ONE ◽

10.1371/journal.pone.0124747 ◽

2015 ◽

Vol 10 (5) ◽

pp. e0124747 ◽

Cited By ~ 18

Author(s):

Maciej Kwiatek ◽

Tomasz Gęca ◽

Arkadiusz Krzyżanowski ◽

Agnieszka Malec ◽

Anna Kwaśniewska

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Regulatory T Cells ◽

Recurrent Miscarriage ◽

First Trimester ◽

Normal Pregnancy

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Proportional changes of CD4+CD25+Foxp3+ Regulatory T cells in maternal peripheral blood during pregnancy and labor at term and preterm

Clinical & Investigative Medicine ◽

10.25011/cim.v33i6.14594 ◽

2010 ◽

Vol 33 (6) ◽

pp. 422 ◽

Cited By ~ 34

Author(s):

Huijuan Xiong ◽

Changju Zhou ◽

Guannan Qi

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Peripheral Blood ◽

Preterm Labor ◽

First Trimester ◽

Normal Pregnancy ◽

Third Trimester ◽

Blood Samples ◽

Maternal Peripheral Blood ◽

Dramatic Decline

Purpose: To evaluate the proportional changes of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in maternal peripheral blood during pregnancy and labor at term and preterm. Methods: Peripheral blood was collected from 20 non-pregnant controls and 139 pregnant women (60 at different gestational ages, 48 at term with or without labor, and 31 in threatened or actual preterm labor). CD4+CD25+Foxp3+ Tregs in peripheral blood samples were analyzed in peripheral blood samples by flow cytometry. Placentas from preterm women were examined for the presence of histological chorioamnionitis (HC). Results: The percentage of circulating CD4+CD25+Foxp3+ Tregs was significantly increased in women during the first trimester compared with non-pregnant controls (P < 0.0001), peaking during the second trimester and then declining slightly in the third trimester. There was a significantly lower level of CD4+CD25+Foxp3+ Tregs in women with term labor than in those at term without labor (P < 0.0001). Women admitted in preterm labor had a lower proportion of CD4+CD25+Foxp3+ cells than those admitted with threatening preterm labor (P < 0.0001). Preterm women with evidence of HC had decreased proportion of CD4+CD25+Foxp3+ cells than those without HC in preterm deliveries (P=0.008). Moreover, the percentages of CD4+CD25+Foxp3+ cells in preterm subjects, irrespective of the HC status, were significantly diminished compared with women with normal pregnancy at the same gestational age (P < 0.0001). Conclusion: Our data reveal a marked elevation of peripheral blood CD4+CD25+Foxp3+ Tregs during early pregnancy, but a dramatic decline during labor, either at term or preterm, suggesting their involvement in the maintenance of pregnancy and the initiation of labor.

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The Fluctuation of Regulatory T Cells during Pregnancy and Obstetrical Complications

10.21203/rs.2.22966/v1 ◽

2020 ◽

Author(s):

Yuan-Yuan Zhao ◽

Ning Li ◽

Hongchu Bao ◽

Nayoung Sung ◽

Xiaolu Zhang ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Pregnant Women ◽

T Cell Activation ◽

Peripheral Blood ◽

Cell Activation ◽

Recurrent Pregnancy Loss ◽

Normal Pregnancy ◽

Phenotypic Characteristics ◽

Complicated Pregnancy

Abstract Background: Regulatory T cells (Tregs) are critical immunomodulators during pregnancy by preventing maternal T-cell activation against fetal cells. However, how characteristics of maternal Tregs vary during pregnancy is still unclear. We analyzed the proportion and phenotypic characteristics of peripheral blood Tregs in normal pregnant women, women with recurrent pregnancy loss (RPL) or gestational diabetes mellitus (GDM), and non-pregnant women.Methods: We investigated the proportion of CD4+ Tregs, CD8+ Tregs and the expression of PD-1, GITR, HLA-G and CTLA-4 on them in the peripheral blood of normal pregnancies during 1st (n = 28), 2nd (n = 43), and 3rd trimester (n = 33); In addition, we evaluated pregnancies in the 1st trimester complicated by RPL (n = 21), in the 2nd (n = 17) and 3rd trimester (n = 28) complicated by GDM. Non-pregnant women (n = 57) were also investigated using flow cytometry.Results: During normal pregnancy, the proportion of CD4+ Tregs in all trimester and CD8+ Tregs in 2nd and 3rd trimester were higher(P ＜ 0.05，respectively) compared with non-pregnancy women. Moreover, the proportion of CD4+ Tregs was higher in 2nd trimester compared to 1st and 3rd trimester (P ＜ 0.01) while the proportion of CD8+ Tregs was higher in 3rd trimester compared to 1st and 2nd trimester (P ＜ 0.05). Compared to non-pregnant studies, the proportion of GITR+/CD8+ Tregs and HLA-G+/CD8+ Tregs in all trimester were higher(P ＜ 0.05, respectively). Moreover, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs, PD-1+/CD8+ Tregs and CTLA-4+/CD8+ Tregs in 3rd trimester were significantly higher compared to 1st, 2nd trimester and non-pregnant group(P ＜ 0.05, respectively).In RPL and GDM groups, the proportions of CD4+ Tregs in all trimesters were decreased while the proportions of CD8+ Tregs in all trimesters were increased compared to normal pregnant group (P ＜ 0.05，respectively).In RPL group, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs and HLA-G+/CD4+ Tregs were decreased compared to 1st trimester normal pregnant group (P ＜ 0.05，respectively). In 2nd trimester GDM group, the proportion of HLA-G+/CD4+ Tregs were decreased compared to 2nd trimester normal pregnant group (P ＜ 0.05，respectively). In 3rd trimester GDM group, the proportion of PD-1+/CD4+ Tregs, GITR+/CD4+ Tregs, PD-1+/CD8+ Tregs, GITR+/CD8+ Tregs and HLA-G+/CD8+Tregs were decreased compared to 3rd trimester normal pregnant group (P ＜ 0.05, respectively).Conclusions: The proportion of CD4+ Tregs and CD8+ Tregs increased during pregnancy, the proportions and subsets of CD4+ Tregs decreased and those of CD8+ Tregs increased in pregnancies complicated by RPL and GDM, indicating that regulatory T cells play a role in pregnancy maintenance, and the abnormal expression of Tregs might be related to the complicated pregnancy.

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