| 1. |
- Ekerfelt, Christina, et al.
(författare)
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Spontaneous secretion of interleukin-4, interleukin-10 and interferon-gamma by first trimester decidual mononuclear cells
- 2002
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Ingår i: American Journal of reproductive immunology. - : Wiley. - 8755-8920 .- 1046-7408. ; 47:3, s. 159-166
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Tidskriftsartikel (refereegranskat)abstract
- PROBLEM: A T-helper cell type 2 (Th2) cytokine dominated microenvironment has been predicted to be crucial for successful pregnancy. However, little information is available about local cytokine secretion in the human decidua. We determined the spontaneous secretion of interleukin-4 (IL-4), interferon-γ (IFN-γ) and IL-10 by decidual mononuclear cells at the single cell level and compared it with their secretion by peripheral blood mononuclear cells (PBMC) in the first trimester of pregnancy. METHODS OF STUDY: The cytokine secretion from decidual and blood cells was detected by a sensitive enzyme-linked immunosorbent spot-forming cell (ELISPOT)-assay. RESULTS: Cells secreting IL-4 (median 153, range 8–530), IL-10 (median 188, range 32–1600) and IFN-γ (median 123, range 15–1140) were detected in all decidual and blood samples. The cytokine secretion showed a co-linear pattern in both the blood and decidua, i.e. when one cytokine was secreted at high levels, the others followed the trend. No correlation was found between the number of cytokine secreting cells in blood and decidua for any of the cytokines. CONCLUSIONS: Interleukin-4 and IL-10 are locally secreted in the decidua early during normal pregnancy, probably counteracting the fetal rejecting effects of co-expressed IFN-γ. The cytokine secretion by blood cells does not generally reflect the local secretion pattern during first trimester pregnancy.
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| 2. |
- Ekerfelt, Christina, 1957-, et al.
(författare)
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Th2-deviation of fetus-specific T cells
- 1999
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Ingår i: Immunology today (Amsterdam. Regular ed.). - 0167-5699 .- 1355-8242. ; 20, s. 534-534
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Gustafsson (Lidström), Charlotte, et al.
(författare)
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Cytokine secretion in decidual mononuclear cells from term human pregnancy with or without labour : ELISPOT detection of IFN-gamma, IL-4, IL-10, TGF-beta and TNF-alpha
- 2006
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Ingår i: Journal of reproductive immunology. - : Elsevier BV. - 0165-0378. ; 71:1, s. 41-56
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Tidskriftsartikel (refereegranskat)abstract
- Cytokines are believed to be important in maintaining pregnancy and in the process of labour induction in humans. The aim of this study was to investigate the secretion of the cytokines interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-10, transforming growth factor-β (TGF-β) and tumour necrosis factor-α (TNF-α) in decidual tissue with or without labour. Decidual tissue was collected from 32 healthy women undergoing elective caesarean sections before the onset of labour (n = 17) or after normal vaginal delivery (n = 15). Mononuclear cells were analysed for cytokine secretion with ELISPOT. To validate the widely used method of tissue collected at caesarean sections and after vaginal deliveries as a representative of before and after labour, respectively, placenta biopsies were collected from 12 healthy women to study the expression of the prostaglandin pathway enzymes cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase (mPGES). Decidual mononuclear cells from term human pregnancy spontaneously secrete IFN-γ, IL-4, IL-10, TGF-β and TNF-α. No difference was seen in cytokine secretion with or without labour, indicating that decidual leukocytes are not the main cell population responsible for plausible cytokine regulation in the process of termination of pregnancy. Placental tissues obtained after vaginal delivery showed a higher mRNA expression of the prostaglandin regulating molecules COX-2 and mPGES than tissues from caesarean sections before the onset of labour, validating that the model can be used as a representative of the state before and after labour.
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| 4. |
- Jonsson, Yvonne, et al.
(författare)
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Cytokine mapping of sera from women with preeclampsia and from women with normal pregnancies
- 2006
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Ingår i: Journal of Reproductive Immunology. - : Elsevier BV. - 0165-0378. ; 70:1-2, s. 83-91
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Preeclampsia is a pregnancy-specific syndrome. The immune system in preeclampsia is changed with an increased innate activity and there is a hypothesis of a shift towards Th1-type immunity. The aim of this study was to determine a spectrum of soluble immunological factors denoting different aspects of immune activation in third trimester sera from women with preeclampsia (N = 15) and compare with levels in sera from normal pregnant women (N = 15). Material and methods IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p40, IL-13, IL-15, IL-17, IFN-α, IFN-γ, TNF-α, GM-CSF, MIP-lα, MIP-1β, MCP-1, eotaxin and RANTES were measured in serum using multiplex bead arrays. The levels of soluble CD14 and soluble IL-4 receptor were measured by enzyme-linked immunoassay (ELISA). Results Preeclamptic women had significantly increased levels of circulating IL-6 (p = 0.002), IL-8 (p = 0.003) and soluble IL-4R (p = 0.037), compared to women with normal pregnancies. Conclusion This study supports the hypothesis of increased inflammatory responses in preeclampsia, illustrated by the increased levels of IL-6 and IL-8. The finding of increased levels of soluble IL-4 receptor is an intriguing finding with several interpretations, which may partly support the hypothesis of a Th1 shift in preeclampsia.
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| 5. |
- Jonsson, Yvonne, et al.
(författare)
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Indications of an altered immune balance in preeclampsia : A decrease in in vitro secretion of IL-5 and IL-10 from blood mononuclear cells and in blood basophil counts compared with normal pregnancy
- 2005
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Ingår i: Journal of Reproductive Immunology. - : Elsevier BV. - 0165-0378. ; 66:1, s. 69-84
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that maladaptation of the maternal immune response during pregnancy might be a causal factor for preeclampsia. This study was designed to examine the systemic immune status at both the innate level and the adaptive level in pregnancies complicated by preeclampsia (n = 15) and normal pregnancies (n = 15). Spontaneous and in vitro-induced secretion of IL-5, IL-6, IL-10, IL-12, IL-13 and TNF-α, in response to paternal blood cells and the vaccination antigens purified protein derivate of tuberculin (PPD) and tetanus toxoid (TT), was detected in cell culture supernatants from blood mononuclear cells by ELISA. Preeclamptic women showed reduced numbers of basophil granulocytes in the blood (p = 0.004) and lower spontaneous secretion of IL-5 from blood mononuclear cells (p = 0.016). In addition, paternal antigen-induced secretion of IL-10 was decreased in preeclampsia compared with normal pregnancy (p = 0.012). No further differences between preeclampsia and normal pregnancy were found for any stimuli or cytokines. The present findings of reduced basophil numbers and lower spontaneous in vitro secretion of IL-5 in preeclampsia compared with normal pregnancy indicate a decrease in systemic Th2 immunity in preeclampsia. Furthermore, the decrease in paternal antigen-induced secretion of the immunosuppressive cytokine IL-10 in preeclampsia indicates a fetus-specific decrease in immunosuppression mediated by blood mononuclear cells. Whether these systemic changes are a cause or a consequence of preeclampsia remains to be elucidated.
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| 6. |
- Jonsson, Yvonne, et al.
(författare)
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Systemic Th1/Th2 cytokine responses to paternal and vaccination antigens in preeclampsia: no differences compared with normal pregnancy
- 2004
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Ingår i: American Journal of Reproductive Immunology. - : John Wiley & Sons. - 1046-7408 .- 1600-0897. ; 51:4, s. 302-310
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Tidskriftsartikel (refereegranskat)abstract
- Problem: A Th1-shift has been suggested to be involved in the pathogenesis of preeclampsia. This study was designed to compare Th1/Th2 related cytokine secretion in blood between women with preeclampsia (n = 15) and normal pregnancies (n = 15), using a high-sensitivity technique for cytokine detection.Methods of study: Spontaneous as well as 'fetus-specific' and recall antigen-specific (purified protein derivate of Mycobacterium tuberculosis, tetanus toxoid and lipopolysaccharide) secretion of interferon-γ, interleukin (IL)-4, IL-10 and IL-12 in peripheral blood mononuclear cells (PBMC) was detected by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT). Fetus-specific secretion was induced by stimulation with paternal PBMC in a mixed leukocyte culture assay.Results: All cytokines were secreted by PBMCs both from women with preeclampsia and women with normal pregnancies. No differences in the number of cytokine-secreting cells were found between the two groups.Conclusions: No evidence was found for a shift in the systemic Th1/Th2 responses, in preeclampsia compared with normal pregnancy. This does, however, not exclude differences in the local immune responses related to the fetoplacental unit.
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| 7. |
- Lidström Gustafsson, Charlotte, et al.
(författare)
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Cytokine secretion patterns of NK cells and macrophages in early human pregnancy decidua and blood : Implications for suppressor macrophages in decidua
- 2003
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Ingår i: American Journal of reproductive immunology. - : Wiley. - 8755-8920 .- 1046-7408 .- 1600-0897. ; 50:6, s. 444-452
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Tidskriftsartikel (refereegranskat)abstract
- Problem: Local immune modulation has been shown to be of considerable importance for the maintenance of successful pregnancy. We have previously reported the secretion of interferon-γ (IFN-γ), interleukin-4 (IL-4) and IL-10 in human decidua from early normal pregnancy. The aim of this study was to investigate the cellular source of cytokine secretion in the decidua, and compare this to secretion patterns in peripheral blood. Method of study: Decidual tissue and peripheral blood was collected from 20 women undergoing surgical abortion during first trimester pregnancy. Monocytes/macrophages and NK cells were enriched by immunomagnetic cell separation and cytokine secretion was detected by enzyme-linked immunosorbent spot-forming cell assay. Results: Decidual and peripheral monocytes/macrophages and NK cells spontaneously secrete IFN-γ, IL-4 and IL-10. The number of IL-10 secreting cells was significantly higher in decidual macrophages compared with decidual non-monocytic cells as well as compared with blood monocytes/macrophages. These differences were not seen for IFN-γ or IL-4. Conclusions: Our results indicate that decidual macrophages subserve important suppressive functions in the pregnant uterus.
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| 8. |
- Matthiesen, Leif, 1954-, et al.
(författare)
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Immunology of preeclampsia
- 2005
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Ingår i: Immunology of pregnancy. - Basel, Switzerland : S. Karger. - 9783805579704 - 9783318012484 ; , s. 49-61
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Bokkapitel (refereegranskat)abstract
- Preeclampsia is a placenta-dependent disorder with both local and systemic anomalies with neonatal and maternal morbidity. It is manifested late in pregnancy, but the onset is during early stages of gestation. The current hypothesis regarding the aetiology of preeclampsia is focused on maladaptation of immune responses and defective trophoblast invasion. Thus, an excessive maternal inflammatory response, perhaps directed against foreign fetal antigens, results in a chain of events including shallow trophoblast invasion, defective spiral artery remodelling, placental infarction and release of pro-inflammatory cytokines and placental fragments in the systemic circulation. During normal pregnancy, trophoblasts interact in the decidua with the unique uterine NK cells, modifying their cytokine repertoire, regulating adhesion molecules and matrix metalloproteinases. The inability of trophoblasts to accomplish these changes might be a critical factor for the onset of preeclampsia. Several cytokines, produced at the maternal-fetal interface, have an impact on trophoblast invasion. It is suggested that deficiency of interleukin-10 may contribute to enhanced inflammatory responses towards the trophoblasts elicited by e.g. tumour necrosis factor-α and interferon-γ. Consequently, trophoblasts subjected to a high rate of apoptosis are hampered in their invasive capacity resulting in defective transformation of spiral arteries, hypoxia, thrombosis and infarction of the placenta. The ensuing infarction of placenta leads to leakage of increasing amounts of placental fragments and cytokines in the maternal circulation and an exaggerated systemic endothelial activation as identified in preeclampsia. So far, treatment of preeclampsia is focused on signs like hypertension, whereas attempts of modifying immune responses may be a possibility in the future.
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| 9. |
- Matthiesen, Leif, 1954-, et al.
(författare)
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In-situ detection of both inflammatory and anti-inflammatory cytokines in resting peripheral blood mononuclear cells during pregnancy
- 2002
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Ingår i: Journal of Reproductive Immunology. - 0165-0378 .- 1872-7603. ; 58:1, s. 49-59
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Local and possibly systemic curtailment of the maternal immune response is important for a successful pregnancy. Although the local milieu at the utero-placental interface is likely to harbor the most prominent alterations, it is suggested, at least in mice, that systemic immunity is also tolerized during pregnancy. In the present study, we investigated mRNA expression of the key immunomodulatory cytokines, interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-a and interferon (IFN)-? during normal pregnancy. Material and methods: In-situ hybridization (ISH) of cytokine mRNA in resting peripheral blood mononuclear cells (PBMCs) was used to detect the number of cells spontaneously expressing cytokines. Eleven women with normal gestations were followed during pregnancy as well as 8 weeks postpartum, and compared with 10 non-pregnant healthy controls. Results: The numbers of IFN-? and IL-4 mRNA expressing cells were found to be significantly increased during pregnancy and postpartum compared with non-pregnant controls. Pregnant women and non-pregnant controls did not differ in their expression of TNF-a and IL-10. Conclusion: Our studies demonstrated increased numbers of both IFN-? and IL-4 mRNA expressing cells in blood suggesting that systemic immunomodulation, albeit partial, takes place during normal pregnancy. It is proposed that enhanced IL-4 expression, possibly in concert with other elevated anti-inflammatory immunomodulatory cytokines, curtail the potentially hazardous effects of IFN-? on systemic immunity during pregnancy.
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| 10. |
- Mjösberg, Jenny, 1980-, et al.
(författare)
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CD4+ CD25+ regulatory T cells in human pregnancy : Development of a Treg-MLC-ELISPOT suppression assay and indications of paternal specific Tregs
- 2007
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Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 120:4, s. 456-466
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Tidskriftsartikel (refereegranskat)abstract
- The current study was aimed at developing a one-way mixed leucocyte culture-enzyme-linked immunospot (MLC-ELISPOT) assay for the study of CD4 + CD25+ regulatory T (Treg) cells and applying this method in the study of antifetal immune reactions during human pregnancy. Twenty-one pregnant women and the corresponding fathers-to-be, and 10 non-pregnant control women and men, participated in the study. CD4+ CD25+ cells were isolated from peripheral blood mononuclear cells (PBMC) by immunomagnetic selection. Maternal/control PBMC were stimulated with paternal or unrelated PBMC in MLC. Secretion of interleukin-4 (IL-4) and interferon-γ (IFN-γ) from responder cells, with or without the presence of autologous Treg cells, was analysed by ELISPOT. PBMC from pregnant women showed increased secretion of IL-4 compared to controls. In pregnant and non-pregnant controls, Treg cells suppressed IFN-γ reactivity against paternal and unrelated alloantigens. Interestingly, T reg cells suppressed IL-4 secretion against paternal but not unrelated alloantigens during pregnancy. We have successfully developed a model for studying Treg cells in antifetal cytokine reactions during pregnancy. Results indicate that Treg cells contribute to strict regulation of both T helper type 1-like and type 2-like antifetal immune reactions. Interestingly, T helper type 2-like cells specific to unrelated alloantigens are able to escape the suppression of Treg cells, which would allow for IL-4, alongside CD4+ CD25+ Treg cells, to control potentially detrimental IFN-γ reactions during pregnancy. © 2007 Blackwell Publishing Ltd.
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