T helper 1- and T helper 2-type cytokine imbalance in pregnant women with pre-eclampsia

Darmochwał-Kolarz, Dorota; Leszczyńska‐Gorzelak, Bożena; Roliński, Jacek; Oleszczuk, Jan

doi:10.1016/s0301-2115(99)00065-2

Cited by 116 publications

(72 citation statements)

References 19 publications

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“…Our results are consistent with a previous study [20], which demonstrated elevated serum levels of granulysin in preeclamptic Japanese women (3.8±1.8 ng/ml in severe preeclamptic cases and 2.6±0.6 ng/ ml in mild cases) as compared with normotensive controls (1.9±0.8 ng/ml). Our results are also compatible with those studies indicating cytotoxic T-cell and natural killer cell are activated in preeclampsia [13] and those in-vitro reports indicting that phytohaemagglutinin (PHA)-stimulated 1L-2 and interferon-γ (IFN-γ) production are significantly higher (P<0.001) in preeclamptic patients than in the controls [26]. IL-2 and IFN-γ are synthesized by Th1 cells.…”

Section: Discussionsupporting

confidence: 93%

Plasma granulysin concentrations and preeclampsia risk

Qiu

Saito

Sakai

et al. 2006

Clinical Biochemistry

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Objective-Epidemiological, clinical and histological data suggest intriguing similarities between preeclampsia and graft-host-rejection. Granulysin, a novel biomarker of overall cellular immunity, is secreted by natural killer cells and cytotoxic T lymphocytes, which are associated with graft-hostrejection. Plasma granulysin was elevated in Japanese preeclamptic women.Design and Methods-50 preeclampsia cases and 50 normotensive controls (USA) were studied. Plasma granulysin at delivery was determined using enzyme immunoassay. Logistic regression procedures were used to estimate odds ratios (OR) and 95% confidence intervals (CI).Results-Granulysin were elevated in preeclampsia cases compared with controls (3.01±0.18 vs. 2.22±0.14 ng/ml, p<0.01). After adjusting for age, body-mass-index and race, women with higher granulysin concentrations (≥1.89 ng/ml) experienced a 2.9-fold (95%CI 1.1-7.8) increased preeclampsia risk compared with women with lower granulysin (<1.89 ng/ml).Conclusions-These data offer further evidence of a predominant Th1 immune status associated with preeclampsia. Prospective studies are needed to determine whether granulysin is elevated early in pregnancy.

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Section: Discussionsupporting

confidence: 93%

Plasma granulysin concentrations and preeclampsia risk

Qiu

Saito

Sakai

et al. 2006

Clinical Biochemistry

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“…Successful pregnancy is associated with decreased cell-mediated responses and an increased rate of Ab production, suggesting an elevated Th2/Th1 immune response (14,15). A key pathway mediating a state of immune tolerance is activation-induced cell death (AICD) 3 (16,17).…”

mentioning

confidence: 99%

Pregnancy-Associated Exosomes and Their Modulation of T Cell Signaling

Taylor

Akyol

Gerçel-Taylor

2006

The Journal of Immunology

263

219

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Exosome release by viable cells is a feature of activated cell types, including tumors, fetal cells, and cells of the immune system. Exosomes critically regulate immune activation, by mediating activation-induced cell death. Fetal cells may mimic these events to selectively delete reactive lymphocytes. In this study the presence and composition of placenta-derived exosomes are demonstrated in the maternal circulation along with their consequences on T cell activation markers. For all pregnant patients, exosomes were isolated from sera obtained between 28 and 30 wk gestation. For pregnant women, subsequently delivering at term, circulating levels of placental exosomes were 1.8 times greater than those delivering preterm (p < 0.0001). Exosomes isolated from pregnancies subsequently delivering at term expressed significantly higher levels of biologically active components, including Fas ligand (FasL) and HLA-DR, than those from pregnancies delivering preterm. Standardizing for protein concentrations, exosomes from term-delivering pregnancies exhibited greater suppression of CD3-ζ and JAK3 than those delivering preterm. The suppression of CD3-ζ and JAK3 correlated with exosome expression levels of FasL (r2 = 0.92 and r2 = 0.938, respectively). Fractionation of exosomes from term-delivering pregnancies by continuously eluting electrophoresis indicated that intact 42kD FasL and an unidentified 24-kDa protein were associated with CD3-ζ suppression. Our results demonstrated that exosomes from pregnancies ultimately delivering at term are present at significantly greater concentrations than those from pregnancies delivering preterm; however, exosomes from term-delivering pregnancies also exhibit significantly greater suppression of CD3-ζ and JAK3.

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“…Transfer of activated immune cells has also been shown to effectively cure malignant tumors in mice [21,32]. Since Th1 cells play a detrimental role during mammalian pregnancy [24][25][26][27] and taking into account the close relationship between activated Th1 immune cells and PE in humans [6,[9][10][11][12][13], we hypothesize that activated Th1 cells will negatively affect late allogeneic, rather than syngeneic, murine gestation and induce PE-like symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…TNF- § , are the stimuli leading to such an immune activation [4][5][6][7][8][9]. A systemic response of activated maternal inflammatory cells (including elevated numbers of granulocytes and monocytes) has been reported in patients suffering from PE [9][10][11], accompanied by increased levels of pro-inflammatory Th1-type cytokines, mainly TNF- § [8,12,13].…”

Section: Introductionmentioning

confidence: 99%

Introducing a mouse model for pre‐eclampsia: adoptive transfer of activated Th1 cells leads to pre‐eclampsia‐like symptoms exclusively in pregnant mice

et al. 2004

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Pre-eclampsia (PE) is the most severe pregnancy-related disease, leading to high maternal and fetal morbidity/mortality. Immunological imbalances associated with endothelial cell dysfunction have been hypothesized as a cause for the onset and perpetuation of PE. Valid and reliable animal models are urgently required to test this hypothesis and to better understand the mechanisms underlying PE. We developed a novel PE-model by adoptively transferring activated BALB/c Th1-like splenocytes into allogeneically pregnant BALB/c female mice during late gestation; the model mimicked the symptoms of PE, i.e. increased blood pressure and glomerulonephritis accompanied by proteinuria. Interestingly, these PE-like symptoms were not detectable in non-pregnant recipients of activated Th1-like cells. Adoptive cell transfer adversely affected the outcome of pregnancy by increasing fetal rejection, with uterine immune cells showing an inflammatory profile. In conclusion, we have established a valid and reliable PE mouse model, which opens vast opportunities for therapeutic interventions.

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T helper 1- and T helper 2-type cytokine imbalance in pregnant women with pre-eclampsia

Cited by 116 publications

References 19 publications

Plasma granulysin concentrations and preeclampsia risk

Plasma granulysin concentrations and preeclampsia risk

Pregnancy-Associated Exosomes and Their Modulation of T Cell Signaling

Introducing a mouse model for pre‐eclampsia: adoptive transfer of activated Th1 cells leads to pre‐eclampsia‐like symptoms exclusively in pregnant mice

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