Expression of Intracellular Th1 and Th2 Cytokines in Women with Recurrent Spontaneous Abortion, Implantation Failures after IVF/ET or Normal Pregnancy

Ng, S.C.; Gilman‐Sachs, Alice; Thaker, Poonam P.; Beaman, Kenneth D.; Beer, Alan E.; Kwak‐Kim, Joanne

doi:10.1034/j.1600-0897.2002.01105.x

Cited by 189 publications

(134 citation statements)

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“…Polyclonally stimulated peripheral blood mononuclear cells from early normal pregnant women produced higher levels of IL-4 and IL-10 and lower levels of IL-2, IFN-c and TNF than women with recurrent miscarriage. 20,21 However, no differences in IL-4-and IFN-c-producing cells were found as compared with non-pregnant women, an observation also made by others 22 but disputed by even others showing higher IL-4 activity in first or third trimester pregnancy as compared with non-pregnant women. 23 Further, IL-10 was…”

mentioning

confidence: 59%

Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance

Ernerudh¹,

Berg²,

Mjösberg³

2011

American J Rep Immunol

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Problem During pregnancy, the maternal immune system needs to adapt in order not to reject the semi-allogenic fetus. Method In this review, we describe and discuss the role of regulatory T (Treg) cells in fetal tolerance. Results Treg cells constitute a T helper lineage that is derived from thymus (natural Treg cells) or is induced in the periphery (induced Treg cells). Treg cells are enriched at the fetal-maternal interface, showing a suppressive phenotype. In contrast, Treg cells are not increased in the circulation of pregnant women, and the suppressive capacity is similar to that in nonpregnant women. However, aberrations in Treg frequencies and functions, both systemically and in the uterus, may be involved in the complications of pregnancy. Conclusion Treg cells seem to have distinguished roles locally versus systemically, based on their distribution and phenotype.

This is the authors’ version of the publication: Jan Ernerudh, Göran Berg and Jenny Mjösberg, Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance, 2011, AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, (66), 31-43. http://dx.doi.org/10.1111/j.1600-0897.2011.01049.x Copyright: John Wiley and Sons http://www.wiley.com/

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confidence: 59%

Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance

Ernerudh¹,

Berg²,

Mjösberg³

2011

American J Rep Immunol

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“…To prevent fetal loss it seems to be necessary to provide a local environment at the fetal-maternal interface that is dominated by Th2 and Th3 immune responses (37). Any changes in favor of the Th1-dominated immune pattern results in a negative outcome of pregnancy (38,39). This might provide one explanation why Th1 immunity, as reflected by the production of IFN-␥, is so extremely low in the neonates and even lower in neonates derived from allergic mothers.…”

Section: Discussionmentioning

confidence: 99%

Critical Role of Preconceptional Immunization for Protective and Nonpathological Specific Immunity in Murine Neonates

Uthoff

Spenner

Reckelkamm

et al. 2003

The Journal of Immunology

111

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Expression of Th2 immunity against environmental Ags is the hallmark of the allergic phenotype and contrasts with the Th1-like pattern, which is stably expressed in healthy adults throughout life. Epidemiological studies indicate that the prenatal environment plays an important and decisive role in the development of allergy later in life. Since the underlying mechanisms were unclear, an animal model was developed to study the impact of maternal allergy on the development of an allergic immune response in early life. An allergic Th2 response was induced in pregnant mice by sensitization and aerosol allergen exposure. Both, IgG1 and IgG2a, but not IgE, Abs cross the placental barrier. Free allergen also crosses the placental area and was detected in serum and amniotic fluids of neonatal F1 mice. These F1 mice demonstrated a suppressed Th1 response, as reflected by lowered frequencies and reduced levels of IFN-γ production. Development of an IgE response against the same allergen was completely prevented early in life. This effect was mediated by diaplacental transfer of allergen-specific IgG1 Abs. In contrast, allergic sensitization against a different allergen early in life was accelerated in these mice. This effect was mediated by maternal CD4 and OVA-specific Th2 cells induced by allergic sensitization during pregnancy. These data indicate a critical role for maternal T and B cell response in shaping pre- and postnatal maturation of specific immunity to allergens.

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“…TNF-a is a pro-inflammatory Th1 cytokine and the ratio of TNF-a producing T cells seems to be significantly higher in patients with recurrent implantation failure (RIF) and RM patients than in fertile controls (Kwak-Kim et al 2003;Ng et al 2002) making it a new treatment target for RM patients. Winger et al (2009) administered TNF-a inhibitors and ivIgGs in combination with low molecular weight heparin (LMWH) in RM patients, which elevated the live birth rate (LBR).…”

Section: Introductionmentioning

confidence: 99%

Granulocyte-Colony Stimulating Factor as Treatment Option in Patients with Recurrent Miscarriage

Santjohanser¹,

Knieper

Franz

et al. 2013

Arch. Immunol. Ther. Exp.

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In 1-5 % of patients during childbearing years recurrent miscarriages (RM) occur. There are established risk factors like anatomical, endocrine and hemostatic disorders as well as immunological changes in the maternal immune system. Nevertheless, further elucidation of the pathogenesis remains a matter of debate. In addition, there are no standardized immunological treatment strategies. Recent studies indicate possible effects of tumor necrosis factor a blocker and granulocyte-colony stimulating factor (G-CSF) concerning live birth rate (LBR) in RM patients. Therefore, we performed a retrospective cohort study in patients undergoing assisted reproductive treatment (ART) with known RM analysing the possible benefits of G-CSF application. From January 2002 to December 2010, 127 patients (199 cylces) with RM (at least 2 early miscarriages) 49 (72 cycles) receiving G-CSF and 78 (127 cycles) controls receiving either no medication (subgroup 1) or Cortisone, intravenous immunoglobulins or low molecular weight heparin (subgroup 2) undergoing ART for in vitro fertilisation/intracytoplasmic sperm injection were analysed. G-CSF was administered weekly once (34 Mill) in 11 patients, 38 patients received 2 9 13 Mill G-CSF per week until the 12th week of gestation. Statistical analysis was performed with SPSS for Windows (19.0), p \ 0.05 significant. The mean age of the study population was 37.3 ± 4.4 years (mean ± standard deviation) and differed not significantly between patients and subgroups. However, the number of early miscarriages was significantly higher in the G-CSF group as compared to the subgroups (G-CSF 2.67 ± 1.27, subgroup 1 0.85 ± 0.91, subgroup 2 0.64 ± 0.74) and RM patients receiving G-CSF had significantly more often a late embryo transfer (day 5) (G-CSF 36.7 %, subgroup 1 12.1 %, subgroup 2 8.9 %). The LBR of patients and the subgroups differed significantly (G-CSF 32 %, subgroup 1 13 %, subgroup 2 14 %). Side effects were present in less than 10 % of patients, consisting of irritation at the injection side, slight leukocytosis, rise of the temperature (\38°C), mild bone pain and hyperemesis gravidarum. None of the newborn showed any kind of malformations. According to our data, G-CSF seems to be a safe and promising immunological treatment option for RM patients. However, with regard to the retrospective setting and the possible bias of a higher rate of late embryo transfers in the G-CSF group additional studies are needed to further strengthen our results.

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Expression of Intracellular Th1 and Th2 Cytokines in Women with Recurrent Spontaneous Abortion, Implantation Failures after IVF/ET or Normal Pregnancy

Cited by 189 publications

References 45 publications

Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance

Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance

Critical Role of Preconceptional Immunization for Protective and Nonpathological Specific Immunity in Murine Neonates

Granulocyte-Colony Stimulating Factor as Treatment Option in Patients with Recurrent Miscarriage

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