Umbilical cord blood CD45+/CD34+ cells coexpression in preterm and full-term neonates: a pilot study

Objective.?Human umbilical cord blood (hUCB) is rich in stem cells. The CD45⁺/CD34⁺ coexpression in hUCB is a marker of hemopoietic progenitor cells. The objective of this study is to compare the coexpression of hUCB CD45⁺/CD34⁺ cells in preterm (PT) and full-term (FT) neonates.

Methods.?We studied the coexpression of hUCB CD45⁺/CD34⁺ cells in PT and FT neonates. The study included 25 PT (29–36 weeks gestation) and 25 FT (37–41) neonates delivered at Ain Shams University, Maternity Hospital. Absolute mononuclear layer cord blood CD45⁺/CD34⁺ cell count were measured by flow cytometry. Morbidity was assessed for 12 of the studied 25 PT infants, using Morbidity Assessment Index for Newborns score.

Results.?The absolute CD45⁺/CD34⁺ count did not differ between PT and FT infants: Z?=??0.485, p?=?0.63. There was no correlation between absolute cell count and GA (r?=?0.013, p?=?0.9) for all 50 neonates. Mode of delivery did not affect the absolute count in the PT infants: Z?=?–0.6, p?=?0.57. There was no correlation between the degree of morbidity and absolute cell count in PT neonates; r?=?0.13, p?=?0.69.

Conclusion.?The absolute cell count is not affected by gestational age and did not relate to morbidity scores in the studied PT infants. Further, wide-scale work will be needed to study CD45⁺/CD34⁺ count in hUCB in sick PT neonates.     

Decreased frequency of peripheral blood CD8+CD25+FoxP3+regulatory T cells correlates with IL-33 levels in pre-eclampsia

Objective: We aimed to investigate the role of CD8⁺CD25⁺Foxp3⁺regulatory T (Treg) cells in pre-eclampsia (PE).

Methods: This was a cross-sectional study of 46 patients with PE and 24 normotensive women within the third trimester of gestation. We analyzed the percentages of CD8⁺CD25⁺Foxp3⁺Treg cells in peripheral blood using flow cytometry and the serum levels of interleukin (IL)-6, IL-17A, IL-10, TGF-β1, IL-1β, and IL-33 by Luminex 200.

Results: We found that patients with PE had lower percentages of CD8⁺CD25⁺Foxp3⁺Treg cells than normotensive pregnant women. In addition, the percentage of CD8⁺CD25⁺Foxp3⁺Treg cells was positively correlated with IL-33 concentration and negatively correlated with IL-17A concentration in patients with PE. We also found that IL-33 treatment can induce proliferation of CD8⁺CD25⁺Foxp3⁺Treg cells in vitro.

Conclusions: These findings suggest that the reduced CD8⁺CD25⁺Foxp3⁺Treg cells may play a role in the pathogenesis of PE.

Abbreviations

PE: pre-eclampsia; PBMCs: peripheral blood mononuclear cells; CTLA-4: cytotoxic T-lymphocyteantigen-4; APCs: antigen presenting cells; TGF-β: transforming growth factor-β; IL: interleukin; Treg: cells regulatory T cells; PBS: phosphate-buffered saline; Foxp3: forkhead Box protein 3; HELLPs: hemolysis, elevated liver enzyme and low platelet syndrome     

What is the role of regulatory T cells in the success of implantation and early pregnancy?

Problem The immune system is well controlled by the balance between immunostimulation and immunoregulation. CD4⁺CD25⁺ regulatory T (Treg) cells and an enzyme called indoleamine-2, 3-dioxygenase (IDO) mediate maternal tolerance of the allogeneic fetus. Treg cells, therefore, may prevent early pregnancy loss due to maternal ‘rejection.’ Methods The latest understanding of tolerance during pregnancy is reviewed. Results and conclusions Recent data show that CD4⁺CD25⁺ Treg cells play essential roles in the induction and maintenance of tolerance, and that they augment the IDO activity in dendritic cells and macrophages. Therefore, CD4⁺CD25⁺ Treg cells and IDO enzyme may cooperate in the induction of tolerance during pregnancy. Treg deficiency is associated with very early post-implantation loss and spontaneous abortion in animal models, and low Treg levels are associated with recurrent miscarriages in humans.     

Decidual CD4+CD25+CD127dim/- regulatory T cells in patients with unexplained recurrent spontaneous miscarriage

Objectives

To investigate the frequency and function of CD4⁺CD25⁺CD127^dim/− regulatory T (Treg) cells in decidua of patients with unexplained recurrent spontaneous miscarriage (URSM).

Study design

The decidual lymphocytes from patients who experienced URSM and normal pregnant women (controls) were collected by Ficoll density gradient centrifugation. CD4⁺CD25⁺CD127^dim/− Treg cells were isolated by magnetic cell sorting. The proportion of Treg cells and IL-10, TGF-β in Treg cells were determined by flow cytometry. Inhibitory effects of Treg cells on effecter T cells were detected with or without the presentation of anti-IL-10 antibodies and anti-TGF-β antibodies.

Results

The frequency of CD4⁺CD25⁺CD127^dim/− Treg cells was decreased in URSM decidua compared to controls (2.09% ± 0.86% vs. 2.97% ± 1.19%, p = 0.005), and the expression of IL-10 and TGF-β in Treg cells was lower in the URSM group than in the control group (p = 0.04 and p = 0.01, respectively). Furthermore, the suppressive effect of CD4⁺CD25⁺CD127^dim/− Treg cells on the proliferation of effector T cells was decreased in URSM decidua (p < 0.05). Suppression was mediated predominantly through IL-10 and TGF-β in decidua.

Conclusions

Decreased frequency and immunosuppressive capacity of CD4⁺CD25⁺CD127^dim/− Treg cells was found in URSM decidua. Treg cells inhibit proliferation of effector T cells mainly via IL-10 and TGF-β in URSM decidua.     

Expression and significance of dendritic cells and Th17/Treg in serum and placental tissues of patients with intrahepatic cholestasis of pregnancy

Purpose: Dendritic cells (DCs) are involved in immune system, which can also regulate the differentiation of T helper 17 (Th17) and regulatory T cells (Treg). DCs and Th17/Treg participate in preeclampsia and recurrent spontaneous abortion (RSA), but there is still lack of research in intrahepatic cholestasis of pregnancy (ICP). The aim was to evaluate the expression and significance of CD83⁺DCs, CD1a⁺DCs, interleukin-17 (IL-17) and IL-35 in serum and placental tissues of patients with ICP.

Methods: Thirty cases of mild ICP, 25 cases of severe ICP were selected, and 30 cases of normal pregnant women were selected as control group. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were used to detect the expression of CD83⁺DCs, CD1a⁺DCs, IL-17 and IL-35 in serum and placenta tissues, respectively.

Results: There were more CD83⁺DCs, IL-17 expressed in placenta from women with ICP than in normal pregnancies, while the number of decidual CD1a⁺DCs, IL-35 was significantly lower in ICP than in normal pregnant women. The comparison within three groups had statistical difference (p?+DCs and CD1a⁺DCs levels had no significance. IL-17 was higher in ICP, while IL-35 was lower.

Conclusions: DCs are involved in damaging the maternal–fetal immune tolerance by changing the phenotype and mature state, which may affect the differentiation of Th17/Treg to cause ICP.     

The Na+/K+ Co-Transport system in erythrocytes from pregnant patients

Summary In erythrocytes, the extrusion of a cellular sodium level load is accomplished by the Ouabain—sensitive Na⁺/K⁺ pump and by the furosemide-sensitive Na⁺/K⁺—cotransport, which operates against the passive sodium permeability. An abnormal low rate of net sodium extrusion by the Na⁺/K⁺ cotransport was observed in pre—eclamptic patients. At the molecular level the cotransport abnormality seems to be the consequence of an apparent diminished affinity for intracellular Na⁺. Normal pregnancy is characterized by a strong increase of Na⁺/K⁺ cotransport efflux. No difference could be detected between the passive sodium permeability of erythrocytes from normotensive pregnant patients and from normotensive non-pregnant controls. Pre-eclampsia seems to be associated with a low passive sodium and potassium permeability. The abnormalities of cotransport and red cell deformability in patients with pre-eclampsia might be interpreted as an early sign of impaired microcirculation and increased vascular reactivity.     

Adoptive transfer of CD4+CD25+ regulatory T cells for prevention and treatment of spontaneous abortion

Objectives

The purpose of this study was to examine whether adoptive transfer with in vitro expanded CD4⁺CD25⁺ regulatory T cells (Tregs) could prevent immune response-mediated spontaneous abortion in mice.

Study design

Female CBA/J mice were mated with male Balb/c as the control with normal pregnancy or with DBA/2J mice as a model of spontaneous abortion. The CBA/J mice mated with DBA/2J were treated intravenously with freshly isolated or in vitro expanded Tregs on day 1 or 4 of pregnancy, respectively. The numbers of surviving and reabsorbed fetuses in the different groups of mice were counted on day 14 of pregnancy, and the concentrations of cytokines in individual sera and the supernatants of cultured Tregs were measured by ELISA.

Results

Adoptive transfer with freshly isolated Tregs only slightly reduced the fetal resorption rate, which was not significantly different from that of the mice without Treg treatment, regardless of treatment at early stage and implementation of pregnancy. In contrast, adoptive transfer with in vitro expanded Tregs significantly reduced the fetal resorption rates, particularly for treatment at early stage of pregnancy (P < 0.05). Furthermore, adoptive transfer with in vitro expanded Tregs at early stage of pregnancy significantly increased the levels of serum IL-10, TGF-β1, and the ratios of IL-10 to IFN-γ.

Conclusions

Our data clearly indicated that adoptive transfer with in vitro expanded Tregs at early stage of pregnancy protected fetuses from spontaneous abortion by re-establishing immune tolerance in mice.     

Prospective cohort study about the lymphocyte subpopulations’ change and impact on the pregnancy outcome in fetal growth restriction

Objective: To evaluate lymphocyte subpopulations’ change and impact on the pregnancy outcome in fetal growth restriction (FGR) through a prospective cohort study. Methods: Sixty singleton pregnancies with FGR and 20 normal pregnant women were enrolled at the third trimester of pregnancy in this study. FGR was defined according to fundal height and abdominal circumference through obstetric examination and ultrasound examination. Third trimester peripheral blood and umbilical cord blood lymphocyte subpopulations were analysed by flow cytometry. The cytotoxic activity of lymphocytes using umbilical cord blood mononuclear activated kill cells as the effector cells, K562 cells as the target cells was measured by MTT deoxidation assay. Results: There were no significant differences about the age, parity, gestational age enrolled, BMI before pregnancy between the FGR and control group. The birth weight, length and head circumference of the neonates from FGR group were less than that from normal control. The percentages of B-lymphocytes in peripheral blood at the third trimester were significantly increased in FGR group compared to that in control group (P < 0.05). In umbilical cord blood, FGR group had a higher percentage of both CD3 and CD4 lymphocyte, lower absolute cell counts and percentage of B-lymphocyte, and higher CD4/CD8 ratio than control group (P < 0.05). Most importantly, the kill cell activity of the lymphocytes in cord blood from FGR group was significantly higher than that from control group (P < 0.05). The significant positive correlations were also found that the percentage and number of B lymphocytes in umbilical cord blood with birthweight, birthlength and birth head circumference, but CD4/CD8 ratio, the kill cell activity in umbilical cord blood had negative correlations with that. The percentage of B lmyphocyte in third trimester and CD4/CD8 ratio, kill cell activity in umbilical cord blood are associated with an increased risk of prematurity and SGA birth, but contrary result was found with the percentage and number of B lmyphocyte in cord blood. Conclusions: Fetal immunological rejection could be involved in the pathogenesis of FGR. The changes of T lymphocyte subpopulations and B-cells, enhanced kill cell activity might cause FGR and preterm birth.     

妊娠中晚期外周血T淋巴细胞亚群和NK细胞的观察

目的 :检测孕妇外周血T淋巴细胞亚群和NK细胞的变化 ,探讨正常妊娠时母体的细胞免疫状态。方法 :健康孕妇 92例按孕周分为 3组 :中孕组 (孕周 13～ 2 7+ 6周 )、晚孕未足月组 (孕周 2 8～ 36 + 6周 )和足月组 (孕周 37～ 4 1+ 6周 ) ;另取同期健康未孕生育年龄妇女 2 0例作对照组。用流式细胞仪检测其外周血T淋巴细胞亚群和NK细胞的相对数 ,结合外周血白细胞计数计算其绝对数。结果 :正常孕妇外周血白细胞总数显著增加 ,其中粒细胞百分数和绝对数均显著增加 ,单核细胞绝对数增加 ,淋巴细胞百分数和绝对数均显著减少 ;CD3+ 细胞百分数显著增加 ,CD4 + 细胞百分数和绝对数均显著减少 ,CD4 + /CD8+ 比值显著下降 ,CD8+ 细胞差异无显著性 ;NK细胞百分数和绝对数均显著减少。随着孕周进展 ,CD4 + 细胞百分数和绝对数均逐渐减少 ,CD4 + /CD8+ 比值逐渐下降 ,中孕组与晚孕未足月组比较 ,差异有显著性 (P <0 .0 5 )。结论 :妊娠期母体细胞免疫功能处于免疫抑制状态 ;随着妊娠进展 ,这种抑制有一定程度的下降。     

Long-term supplementation of Rhodiola kirilowii extracts during pregnancy and lactation does not affect mother health status

Antibiotics treatment during pregnancy and lactation is problematic. The alternative to the antibiotic treatment is the use of plant-derived supplements, which stimulate immune system to prevent and eliminate bacterial infection. Here, we evaluated the effect of long-term use of Rhodiola kirilowii on the health of mouse mothers. Pregnant mice were fed daily, for whole pregnancy and for 28 days after giving birth, with Rhodiola kirilowii water (RKW) or hydroalcoholic extract (RKW-A) (at 20?mg of extracts/kg). The control group received sterile water. There was no significant change in the total body weight and selected organs weight and in the status of macroscopically evaluated liver, spleen, kidney, brain, and eyes, between the Rhodiola kirilowii groups and the control group. There was also no change in hematological parameters and components of adaptive immunity (level of CD3⁺, CD4⁺, CD8⁺, CD19⁺, CD335⁺ cells). Mice fed with RKW extracts exhibited lower percentage of oxidative burst in the granulocytes. In contrast, the supplementation with RKW-A extract caused increase in the percentage of granulocytes in the blood and the percentage of monocytes with oxidative burst. Other studied components of innate immunity were unaffected. Minor effect on the innate immunity and lack of side effects on hematological parameters and components of immunological system of mouse mothers indicates that both water and 50% hydroalcoholic extracts of Rhodiola kirilowii (in concentration 20?mg/kg per day) could be used as an immunostimulators during pregnancy and nursing. However, to fully assess the effects of Rhodiola kirilowii extracts on the mother and offspring health, further studies in mouse and large animal models and clinical studies in humans are necessary.     

Abnormal cervical cytology among HIV-positive women in Nigeria

Objective

To determine the prevalence of abnormal cervical smears and high-grade lesions among HIV-positive and HIV-negative women, and to assess the relationship between severity of disease and CD4 count.

Methods

In a prospective cross-sectional comparative study, 250 HIV-positive and 250 HIV-negative women attending the University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria, were enrolled between January and March 2012. Cervical smear samples were collected from participants, examined, and reported via the Bethesda system. Data management and analysis was done with SPSS. Differences between the 2 study groups were determined by χ² test and Student t test.

Results

The prevalence of abnormal cervical smears was significantly higher among HIV-positive women (34.4%) than among HIV-negative women (20.2%) (P < 0.01). The proportion of high-grade lesions was significantly higher among HIV-positive women (23.5%) than among HIV-negative women (8.2%) (P = 0.025). HIV-positive women with a CD4 count below 500 cells/mm³ had significantly more abnormal cervical smears (28.3%) compared with those with a CD4 count of 500 cells/mm³ or more (6.1%) (P = 0.04).

Conclusion

HIV-positive women were found to be at significantly greater risk of developing abnormal cervical cytology and high-grade lesions compared with HIV-negative women.     

Hypertension,inflammation and T lymphocytes are increased in a rat model of HELLP syndrome

Objective: An animal model of hemolysis, elevated liver enzymes, low platelet count (HELLP) was used to determine if T lymphocytes accompany hypertension and increased inflammatory cytokines. Methods: sFlt-1 (4.7?µg/kg/day) and sEndoglin (7?µg/kg/day) were infused into normal pregnant rats (HELLP rats) for 8 days. Results: HELLP was associated with increased mean arterial pressure (p?=?0.0001), hemolysis (p?=?0.044), elevated liver enzymes (p?=?0.027), and reduced platelets (p?=?0.035). HELLP rats had increased plasma levels of TNFα (p?=?0.039), IL-6 (p?=?0.038) and IL-17 (p?=?0.04). CD4⁺ and CD8⁺ T lymphocytes were increased. Conclusion: These data support the hypothesis that T cells are associated with hypertension and inflammation.     

Pregnancy-associated changes in peripheral blood lymphocyte subpopulations in normal Kuwaiti women.

It has recently been reported that healthy pregnancy is associated with systemic immunosuppression. The aim of this study was to evaluate the numbers and distribution of lymphocyte subpopulations in normal, healthy pregnant Kuwaiti women. Thirty-four healthy normotensive women in the 3rd trimester of pregnancy were studied using flow cytometry to define lymphocyte subpopulations and were compared with 16 non-pregnant women. A decrease in the absolute numbers of lymphocytes was observed affecting T cells (CD3+, CD4+, CD8+), B cells (CD19+), and natural killer cells (CD16+/CD56+). When analyzed as a percentage of the total lymphocyte population, there was a significant decrease in B cells and an increase in CD4+ T cells. The T cell population revealed increased expression of CD25 on CD4+ and CD8+ cells, of HLA-DR on CD8+ cells, and of CD54 on CD4+ T cells. The reduced number of lymphocytes suggests that Kuwaiti females may be immunosuppressed in the 3rd trimester of pregnancy. The presence of activated CD4+ T cells could indicate the expression of a regulatory suppressor T cell population, as Treg cells are CD4+CD25+, and suppressor T cells are thought to be CD8+. Future work is required to explore the significance of these T cell populations in pregnancy.     

Phenotypic characterization of regulatory T cells populations in maternal blood,cord blood and placenta from diabetic mothers

Purpose: Changes in regulatory T cells (Treg) in peripheral blood are associated with a number of pathologies, including diabetes. However, the immunological responses of pregnant diabetic women remain scarcely known, and the effects of Treg cells in these patients have yet to be investigated. The present study characterized the expression of regulatory T cells in the maternal blood, cord blood and placenta of diabetic pregnant women.

Materials and methods: The women were divided according to glycemic status into a non-diabetic (ND; N?=?20) or type 2 diabetic (T2DM; N?=?20) group. Cell subsets were determined by flow cytometry.

Results: Compared to ND, T2DM blood cells exhibited a higher expression of CD25⁺, Foxp3⁺, CD4⁺CD25⁺, CD4⁺Foxp3⁺ and CD25⁺Foxp3⁺; and cord blood cells showed a lower expression of CD25⁺, CD4⁺Foxp3⁺ and CD25⁺Foxp3⁺. In the placenta of T2DM, the villous layer of the proportion, CD3⁺ and CD25 was lower than that of CD4⁺Foxp3⁺ and CD25⁺Foxp3⁺, and the extravillous placenta layer contained the lowest levels of CD4⁺ and CD25⁺ and highest proportions of CD4⁺Foxp3⁺. In maternal blood from T2DM, the frequency of CD3⁺CD95⁺ and CD3CD4⁺ T cells expressing CD95⁺ was lower. In cord blood from T2DM, the rate of CD3⁺CD95⁺ was lower. The placenta villous layer of T2DM showed a lower count of CD3⁺CD95⁺ and of CD3CD4⁺ T cells expressing CD95⁺, whereas the number of cells expressing CD3⁺CD45RO⁺ decreased in both placental layers.

Conclusion: The data obtained suggest that hyperglycemia changes the phenotypes of regulatory T cells and Fas expression in memory T cells.     

Reduction of maternal circulating endothelial progenitor cells in human pregnancies with intrauterine growth restriction

Introduction

Circulating endothelial progenitor cells (EPCs) may play a crucial role during pregnancy by sustaining adequate placentation and fetal growth. Unambiguous demonstration of EPC increase during pregnancy has been hampered so far by lack of standardized methods for EPC quantification. In this study we used the currently most accepted phenotype for EPC detection for investigating whether maternal circulating EPCs might increase during normal pregnancy and whether they may fail to increase in pregnancy complicated by idiopathic intrauterine growth restriction (IUGR), a leading cause of perinatal mortality and morbidity characterized by insufficient placental perfusion.

Methods

Twenty-one non-pregnant women, 44 women during healthy pregnancy progression (9, 13 and 22 women in the first, second and third trimester, respectively) and 11 with pregnancy complicated by idiopathic IUGR were recruited in a cross-sectional study. EPCs in maternal blood were identified as CD45^dim/CD34⁺/KDR⁺ cells by flow cytometry. Plasmatic cytokines were measured by ELISA.

Results

We observed a significant and progressive increase of EPCs in normal pregnancy, yet detectable in early pregnancy but even more pronounced in the third trimester. The increase of EPCs was impaired in IUGR-complicated pregnancies at comparable gestational age. The circulating levels of placental growth-factor and stromal-derived-factor-1 were significantly lower in IUGR than normal pregnancies, possibly contributing to EPC impairment.

Conclusions

EPC count in maternal circulation may have a great potential as a novel biomarker for pregnancy monitoring and may represent the target of novel therapeutic strategies designed to prevent adverse pregnancy outcomes often occurring in IUGR.     

Synthesis of IFN-γ by CD8 T Cells Is Preserved in HIV-Infected Women with HPV-Related Cervical Squamous Intraepithelial Lesions

Objective. The aim of this study was to investigate whether coinfection with HIV affects the synthesis of Th1 and Th2 cytokines by peripheral blood T cells of women infected with human papillomavirus (HPV).Methods. Cervical swabs and peripheral blood were obtained from women referred for colposcopy. HPV DNA by Digene's hybrid capture assay, HIV RNA by Roche's Amplicor assay, and cytokine synthesis of T-cell subsets by flow cytometry were assessed. HPV-associated cervical and HIV-associated immune deficiency diseases were staged using the Bethesda System and the Centers for Disease Control criteria, respectively.Results. Patients with HIV and/or HPV infections had lower percentages of IL-2⁺ and higher percentages of IL-10⁺ T cells than healthy women. Furthermore, women with both virus infections (HIV⁺/HPV⁺) had significantly fewer IL-2⁺ CD4⁺, IFN-γ⁺ CD4⁺, and TNF-α⁺ CD4⁺ T cells than women with HPV infection alone (HPV⁺). Whereas HIV⁺ and healthy women had similar numbers of IFN-γ⁺ CD8⁺ T cells, HPV⁺ women had significantly fewer IFN-γ⁺ CD8⁺ T cells than healthy women.Conclusion. HIV infection adversely affects the synthesis of Th1 cytokines by CD4⁺, but not IFN-γ synthesis by CD8⁺ T cells of women with active HPV infection. The increase in IFNγ⁺ CD8⁺ T cells, a phenotype consistent with cytotoxic T lymphocytes, may account for the stable HIV disease of the women studied. However, the increase in IFN-γ⁺ CD8⁺ T cells is less likely to be HPV-specific as there was a higher incidence of HPV-related cervical SIL in HIV⁺/HPV⁺ women compared with HPV⁺ women.     

Alterations in the cellular component of the maternal immune system in a murine preterm delivery model

Abstract

Objective: Investigate changes in the cellular component of maternal immune system in a murine preterm delivery (PTD) model.

Methods: C57BL/6?J mice were mated and on day 14.5 after plugging either whole blood was harvested or Escherichia coli lipopolysaccharide (LPS) was intraperitoneally injected. PTD resulted within 24?h. Ten to twelve hours after LPS injection (initiation of labor), whole blood was harvested. Annexin-V, CD3, CD4, CD8, CD80 and CD86 were counted after running through flow cytometer with gating for mononuclear cells. Control group consisted of non-pregnant mice.

Results: Rate of apoptosis of monocytes and lymphocytes and expression of CD80⁺ and CD86⁺ was increased in non-pregnant mice after LPS injection (p?=?0.009, p?=?0.002, p?<?0.001 and p?=?0.005, respectively), but remained unaltered in pregnant mice. Expression of CD3⁺/4⁺ and CD3⁺/8⁺ on lymphocytes was increased after LPS injection in both pregnant (p?=?0.001, p?=?0.011, respectively) and non-pregnant mice (p?=?0.008, p?<?0.001, respectively).

Conclusions: Cellular component of maternal non-specific immune system is remain suppressed in pregnant mice, whereas specific immune responses of pregnant mice to infection are similar to these of non-pregnant mice.     

The association of HLA-G and immune markers in recurrent miscarriages

Objective: To determine role of human leukocyte antigen (HLA)-G, CD8, CD16, CD56, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α for recurrent miscarriages in feto–maternal interface.

Method: Chorion and decidua samples were obtained from 11 women with unwanted pregnancies (healthy pregnancy, HP) and 10 women with missed abortion diagnosis after at least two pregnancy losses (recurrent miscarriage, RM). In addition, endometrial tissues were obtained from 10 non-pregnant women (NonP). The expressions of markers were evaluated using the Western blot analysis. The values obtained between different groups were compared.

Results: The highest protein expression of CD56 was found in the HP compared to NonP and RM. Meanwhile, the lowest protein expression of CD16 was observed in the NonP compared to HP and RM. The HLA-G expression exhibited the highest level in HP; however, there was no statistically significant difference between groups. CD8 and IFNγ expressions were lowest in the NonP group; however, TNF-α was highest in the RM group.

Conclusions: The CD56 expression of uterine NK cells may be an indicator of a HP. However, not statistically significant, the increased expression of CD16, CD8, and also significantly increased expression of TNF may be associated with the predominant cytotoxic activity in the maternal immune system in patients with RM. Although there was no change in the expression of HLA-G, this finding may mean that the maternal immune system is unresponsive to HLA-G-mediated immunosuppressive signals originating from the fetus in these cases.     

Activated (HLA-DR) T-Lymphocyte Subsets in Early Epithelial Ovarian Cancer and Malignant Ovarian Germ Cell Tumors

We examined peripheral blood T-lymphocyte subsets before initiation of therapy in 79 healthy controls, 3 patients with endometriosis, 95 patients with common epithelial tumors of the ovary, 15 patients with ovarian germ cell tumors, and 3 patients with ovarian sex cord-stromal tumors. In stage Ia/Ib patients with epithelial ovarian cancer, the percentages of activated CD4⁺ (CD4⁺HLA-DR⁺) T cells and activated CD4+ T cells in the CD4⁺ T-cell subsets were significantly higher than those of healthy controls and patients with benign or borderline epithelial tumors of the ovary. These immonologic parameters were subsequently decreased in patients in stage Ic and more advanced stages. In malignant ovarian germ cell tumors, a similar increase in the CD4⁺ T-cell subsets was observed. Moreover, the percentage of activated CD8⁺ T cells in the CD8⁺ T-cell subsets in stage Ia/Ib patients increased significantly compared with those in healthy controls and patients with benign tumors. Our findings indicate that activated T lymphocytes may play some roles in oncogenesis and progression of both epithelial ovarian cancer and malignant ovarian germ cell tumors.     

Inhibition of Na+,K+-ATPase in the hypothalamus,pons and cerebellum of the offspring rat due to experimentally-induced maternal hypothyroidism

Neurodevelopment is known to be particularly susceptible to thyroid hormone insufficiency and can result in extensive structural and functional deficits within the central nervous system (CNS), subsequently leading to the establishment of cognitive impairment and neuropsychiatric symptomatology. The current study evaluated the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism (as a suggestive multilevel experimental approach to the study of hypothyroidism-induced changes that has been developed and characterized by the authors) on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a CNS region-specific manner. The activities of acetylcholinesterase (AChE), Na⁺,K⁺-ATPase and Mg²⁺-ATPase in the offspring hypothalamus, cerebellum and pons were assessed. The study demonstrated that maternal exposure to PTU (0.05% w/v in the drinking water) during the critical periods of neurodevelopment can result in an inhibition of hypothalamic, pontine and cerebellar Na⁺,K⁺-ATPase; a major marker of neuronal excitability and metabolic energy production as well as an important regulator of important systems of neurotransmission. On the other hand, no significant changes in the activities of the herein offspring CNS regions’ AChE and Mg²⁺-ATPase were recorded. The observed Na⁺,K⁺-ATPase inhibition: (i) is region-specific (and non-detectable in whole brain homogenetes), (ii) could constitute a central event in the pathophysiology of clinically-relevant hypothyroidism-associated developmental neurotoxicity, (iii) occurs under all examined experimental schemes, and (iv) certainly deserves further clarification at a molecular and histopathological level. As these findings are analyzed and compared to the available literature, they also underline the need for the adoption and further study of Na⁺,K⁺-ATPase activity as a consistent neurochemical marker within the context of a systematic comparative study of existing (and novel) simulation approaches to congenital and early age hypothyroidism.