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

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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Plasma kisspeptin is raised in patients with gestational trophoblastic neoplasia and falls during treatment

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00555.2005 ◽

2006 ◽

Vol 291 (5) ◽

pp. E878-E884 ◽

Cited By ~ 47

Author(s):

Waljit S. Dhillo ◽

Philip Savage ◽

Kevin G. Murphy ◽

Owais B. Chaudhri ◽

Michael Patterson ◽

...

Keyword(s):

Reproductive Development ◽

First Trimester ◽

Normal Pregnancy ◽

Gestational Trophoblastic Neoplasia ◽

Third Trimester ◽

Blood Samples ◽

Amino Acid Peptide ◽

The Third ◽

First Trimester Of Pregnancy ◽

G Protein Coupled

Kisspeptin is a 54-amino acid peptide, encoded by the anti-metastasis gene KiSS-1, that activates G protein-coupled receptor 54 (GPR54). The kisspeptin-GPR54 system is critical to normal reproductive development. KiSS-1 gene expression is increased in the human placenta in normal and molar pregnancies. Circulating kisspeptin is dramatically increased in normal pregnancy, but levels in GTN have not previously been reported. The present study was designed to determine whether plasma kisspeptin levels are altered in patients with malignant GTN. Thirty-nine blood samples were taken from 11 patients with malignant GTN at presentation during and after chemotherapy. Blood was also sampled from nonpregnant and pregnant volunteers. Plasma kisspeptin IR and hCG concentrations were measured. Plasma kisspeptin IR concentration in nonpregnant ( n = 16) females was <2 pmol/l. Plasma kisspeptin IR in females was 803 ± 125 pmol/l in the first trimester of pregnancy ( n = 13), 2,483 ± 302 pmol/l in the third trimester of pregnancy ( n = 7), and <2 pmol/l on day 15 postpartum ( n = 7). Plasma kisspeptin IR and hCG concentrations in patients with malignant GTN were elevated at presentation and fell during and after treatment with chemotherapy in each patient (mean plasma kisspeptin IR: prechemotherapy 1,363 ± 1,076 pmol/l vs. post-chemotherapy <2 pmol/l, P < 0.0001; mean plasma hCG: prechemotherapy 227,191 ± 152,354 U/l vs. postchemotherapy 2 U/l, P < 0.0001). Plasma kisspeptin IR strongly positively correlated with plasma hCG levels ( r2= 0.99, P < 0.0001). Our results suggest that measurement of plasma kisspeptin IR may be a novel tumor marker in patients with malignant GTN.

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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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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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The Frequency of Peripheral Blood CD4+ CD25high FoxP3+ and CD4+ CD25− FoxP3+ Regulatory T Cells in Normal Pregnancy and Pre-Eclampsia

American Journal of Reproductive Immunology ◽

10.1111/j.1600-0897.2012.01145.x ◽

2012 ◽

Vol 68 (2) ◽

pp. 175-180 ◽

Cited By ~ 60

Author(s):

Gergely Toldi ◽

Shigeru Saito ◽

Tomoko Shima ◽

Amrita Halmos ◽

Zoltán Veresh ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Peripheral Blood ◽

Normal Pregnancy

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Differentiation of memory cells in the T-helper subset during normal pregnancy andpreeclampsy

Journal of obstetrics and women s diseases ◽

10.17816/jowd622110-116 ◽

2013 ◽

Vol 62 (2) ◽

pp. 110-116 ◽

Cited By ~ 2

Author(s):

Anna Vldimirovna Kudryashova ◽

Natalya Yuryevna Sotnikova ◽

Irina Aleksandrovna Panova ◽

Lyudmila Viktorovna Kadyrova

Keyword(s):

Peripheral Blood ◽

First Trimester ◽

Normal Pregnancy ◽

Th2 Cells ◽

Memory Cells ◽

Second Trimester ◽

T Helper ◽

Third Trimester ◽

The Third ◽

High Level

The amount of Th1и and Th2 cells in the peripheral blood increased in the first trimester and remained at the high level during all the process of gestation. Changes in the quantity of memory cells were defined: by the enhanced level of Temra in the CD4+ subset and of IFNγ+ cells in the population of CD4+ Temra in the second trimester; by restoring the balance of Tcm, Tem and Temra to the values of nonpregnant donors in the third trimester. In preeclampsy pregnancy the level Th1, Th2 and IFNγ+ cells in CD4+ population of Temra was significantly higher then in normal pregnancy.

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Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Life ◽

10.3390/life11030245 ◽

2021 ◽

Vol 11 (3) ◽

pp. 245

Author(s):

Daniil Shevyrev ◽

Valeriy Tereshchenko ◽

Elena Blinova ◽

Nadezda Knauer ◽

Ekaterina Pashkina ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

Autoimmune Diseases ◽

Peripheral Blood ◽

Treg Cells ◽

Homeostatic Proliferation ◽

Suppressive Activity ◽

Healthy Donors

Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the functional activity of Tregs stimulated by HP cytokines from patients with rheumatoid arthritis as compared with that of those from healthy donors. Since T cell receptor (TCR) signal strength determines the intensity of HP, we imitated slow HP using IL-7 or IL-15 and fast HP using a combination of IL-7 or IL-15 with anti-CD3 antibodies, cultivating Treg cells with peripheral blood mononuclear cells (PBMCs) at a 1:1 ratio. We used peripheral blood from 14 patients with rheumatoid arthritis and 18 healthy volunteers. We also used anti-CD3 and anti-CD3 + IL-2 stimulation as controls. The suppressive activity of Treg cells was evaluated in each case by the inhibition of the proliferation of CD4+ and CD8+ cells. The phenotype and proliferation of purified CD3+CD4+CD25+CD127lo cells were assessed by flow cytometry. The suppressive activity of the total pool of Tregs did not differ between the rheumatoid arthritis and healthy donors; however, it significantly decreased in conditions close to fast HP when the influence of HP cytokines was accompanied by anti-CD3 stimulation. The Treg proliferation caused by HP cytokines was lower in the rheumatoid arthritis (RA) patients than in the healthy individuals. The revealed decrease in Treg suppressive activity could impact the TCR landscape during lymphopenia and lead to the proliferation of potentially self-reactive T cell clones that are able to receive relatively strong TCR signals. This may be another explanation as to why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease in Treg proliferation under IL-7 and IL-15 exposure can lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis in the case of lymphopenia.

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Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis

Open Medicine ◽

10.1515/med-2021-0285 ◽

2021 ◽

Vol 16 (1) ◽

pp. 826-832

Author(s):

Jiarong Wang ◽

Liansheng Qiu ◽

Yimin Chen ◽

Minyun Chen

Keyword(s):

T Cells ◽

Allergic Rhinitis ◽

Retrospective Study ◽

Regulatory T Cells ◽

Visual Analog Scale ◽

Peripheral Blood ◽

Sublingual Immunotherapy ◽

Analog Scale ◽

Vas Score ◽

Medication Score

Abstract Background Few studies investigated the effects of sublingual immunotherapy (SLIT) on the peripheral regulatory T cells (Tregs)/Th17 ratio. Objective To investigate the effectiveness of SLIT in children with allergic rhinitis (AR) and the effects on the Tregs/Th17 ratio. Methods This was a retrospective study of children who were treated for AR between April 2017 and March 2018 at one hospital. The patients were grouped according to the treatments they received: SLIT + pharmacotherapy vs pharmacotherapy alone. Results Eighty children (51 boys and 29 girls; 40/group) were included. The visual analog scale (VAS) and medication scores at 1 year in the SLIT + pharmacotherapy group were 2.70 ± 1.08 and 1.1 ± 0.8, respectively, which were lower than at baseline (7.7 ± 1.2 and 3.6 ± 1.0, respectively) (both Ps < 0.05). For the pharmacotherapy group, the VAS score was decreased at 1 year vs baseline (3.3 ± 1.2 vs 7.4 ± 1.0; P < 0.05), but the medication score did not change (P > 0.05). In the SLIT + pharmacotherapy group, the Treg percentage increased, while the Th17 percentage decreased at 1 year (both Ps < 0.01). The percentages of Tregs and Th17s did not change in the pharmacotherapy group (both Ps > 0.05). Conclusions SLIT + pharmacotherapy can increase the Treg percentage and decrease the Th17 percentage in the peripheral blood of children with AR.

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Isolation of functional human regulatory T cells (Treg) from the peripheral blood based on the CD39 expression

Journal of Immunological Methods ◽

10.1016/j.jim.2009.05.004 ◽

2009 ◽

Vol 346 (1-2) ◽

pp. 55-63 ◽

Cited By ~ 106

Author(s):

Magis Mandapathil ◽

Stephan Lang ◽

Elieser Gorelik ◽

Theresa L. Whiteside

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Peripheral Blood

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Increased Density of Human Immunodeficiency Virus Type 1 Coreceptors CCR5 and CXCR4 on the Surfaces of CD4+ T Cells and Monocytes of Patients with Schistosoma mansoni Infection

Infection and Immunity ◽

10.1128/iai.71.11.6668-6671.2003 ◽

2003 ◽

Vol 71 (11) ◽

pp. 6668-6671 ◽

Cited By ~ 58

Author(s):

W. Evan Secor ◽

Amil Shah ◽

Pauline M. N. Mwinzi ◽

Bryson A. Ndenga ◽

Caroline O. Watta ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Cell Surface ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Peripheral Blood ◽

Chemokine Receptors ◽

Blood Samples ◽

Immunodeficiency Virus

ABSTRACT Distribution of chemokine receptors CCR5 and CXCR4, which are also coreceptors for human immunodeficiency virus type 1 invasion of cells, was measured on the surfaces of CD4+ T cells and monocytes in peripheral blood samples from a group of Kenyan car washers. Patients with active schistosomiasis displayed higher cell surface densities of these receptors than did cured schistosomiasis patients.

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