Pre‐eclampsia is not Associated with Changes in the Levels of Regulatory T Cells in Peripheral Blood

Sakai

et al. 2006

Clinical Biochemistry

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.

Section: Discussioncontrasting

confidence: 57%

Plasma granulysin concentrations and preeclampsia risk

Qiu

Sakai

et al. 2006

Clinical Biochemistry

The Journal of Immunology

“…1). CD4 ϩ CD25 high T cells have been reported to increase in pregnant mice (6,28,29) and throughout human pregnancy (9,10,30), although others found no significant difference between nonpregnant controls, healthy pregnancy, and preeclampsia (12,13). However, human Treg cells are poorly defined by this marker combination.…”

Section: Discussionmentioning

confidence: 96%

“…Whether deficiencies in the number or function of Treg cells are implicated in the development of preeclampsia remains controversial. Two recent reports described decreased numbers of Treg cells in preeclampsia compared with normal pregnancy (10,11), whereas others found comparable frequencies (12,13).…”

mentioning

confidence: 99%

Systemic Increase in the Ratio between Foxp3+ and IL-17-Producing CD4+ T Cells in Healthy Pregnancy but Not in Preeclampsia

Santner-Nanan¹,

Peek

Khanam³

et al. 2009

417

333

Preeclampsia is the leading cause of morbidity and mortality in pregnancy. Although the etiology of preeclampsia is still unclear, it is believed to involve rejection of the fetus, possibly due to an imbalance between regulatory (Treg) and effector T cells. To test this, we compared the frequencies of circulating CD4+ T cells expressing Foxp3, IFN-γ, IL-10, or IL-17 at the end of the third trimester of healthy and preeclamptic pregnancies. The size of the Treg cell compartment, defined by the frequency of CD4+CD25high, CD4+CD127lowCD25+, and CD4+Foxp3+ cells was significantly higher in normal compared with preeclamptic pregnancies. CD4+CD25high and CD4+CD127lowCD25+ populations in preeclampsia were not significantly different from those in nonpregnant controls, whereas CD4+Foxp3+ cells numbersre slightly lower in preeclampsia. The suppressive activity of ex vivo-sorted CD4+CD127lowCD25+ Treg cells was not significantly different between the three study groups. The percentage of CD4+IL-17-producing T cells decreased significantly in healthy compared with preeclamptic pregnancies and nonpregnant controls, whereas CD4+IL-10- and CD4+IFN-γ-producing cells remained unchanged. Consequently, the ratio of Foxp3+ Treg to IL-17-expressing CD4+ T cells was significantly increased in healthy but not in preeclamptic pregnancies. Thus, preeclampsia is associated with the absence of normal systemic skewing away from IL-17 production toward Foxp3+ expression. Finally, preeclamptic women had significantly higher levels of soluble endoglin, an inhibitor of TGF-β receptor signaling, which may bias toward IL-17 production. These results suggest that homeostasis between regulatory and proinflammatory CD4+ T cells might be pivotal for the semiallogeneic fetus to be tolerated within the maternal environment.

“…17,37,38 Recent reports described decreased numbers of Treg cells in preeclampsia, 53,54 although two other articles found stable Treg cells in preeclampsia. 55,56 However, the sample number was too small in one study, 56 and the other study 55 Recently, the developmental and functional links between induced Treg (iTreg) cells and Th17 cells have been reported. 8,9 Th17 cells and iTreg cells share a requirement for TGF-b, and high TGF-b concentrations induce Treg cells.…”

Section: Th1 ⁄ Th2 ⁄ Th17 and Treg Paradigms In Preterm Labormentioning

confidence: 99%

REVIEW ARTICLE: Th1/Th2/Th17 and Regulatory T‐Cell Paradigm in Pregnancy

Nakashima

et al. 2010

American J Rep Immunol

1,002

833

Citation Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T‐cell paradigm in pregnancy. Am J Reprod Immunol 2010T‐helper (Th) cells play a central role in modulating immune responses. The Th1/Th2 paradigm has now developed into the new Th1/Th2/Th17 paradigm. In addition to effector cells, Th cells are regulated by regulatory T (Treg) cells. Their capacity to produce cytokines is suppressed by immunoregulatory cytokines such as transforming growth factor (TGF)‐β and interleukin (IL)‐10 or by cell‐to‐cell interaction. Here, we will review the immunological environment in normal pregnancy and complicated pregnancy, such as implantation failure, abortion, preterm labor, and preeclampsia from the viewpoint of the new Th1/Th2/Th17 and Treg paradigms.