| Background and Objective Preeclamsia is a common third-trimester pregnant complication which can seriously endanger the health of both the pregnant woman and the fetus, while the etiology and pathogenesis of the disease are still not clear. At present, there are two kinds of assumptions which were generally accepted, including immunology hypothesis and placenta ischemia hypothesis. Among them, immune balance disorders mediated by each distinct subset of CD4+T lymphocytes and their related cytokines are the study hotspot in the past few years. Previous studies suggest that the immune balance between Th (T helper) 1 and Th2 cell is the important mechanism to maintain the immune balance of the pregnant women and the fetus in normal pregnancy. A successful pregnancy depends on the maternal humoral immune-tolerant status mediated by Th2 cells. While the balance of Thl/Th2 is disturbed, it will lead to occurrence of a lot of pregnancy complications such as abortion, premature delivery, preeclampsia. Th17 cells and CD4+CD25+ Foxp3+ regulatory T (Treg) cells are two distinct subpopulations of CD4+T lympho-cytes from Thl and Th2 cells that gained more research and development quickly in recent years, which also play important roles in maintaining the organic immune balance. The exact interaction between fully differentiated Th17 cells and Tregs is presently unclear, but an interesting phenomenon was founded that Thl7 cells and Treg cells show opposite pattern in both differentiation mechanism and biological functions. Some researches show that the Th17/Treg imbalance has participated in the occurrence and development of a lot of inflammatory responses and autoim-mune diseases. It is not unreasonable to extrapolate that the mechanism which can maintain both maternal immune balance and mother-fetal two-way immune balances no longer seems to be confined to the simple Thl/Th2 paradigms, but has developed into the new Th1/Th2/Th17 and Treg paradigms.Until now, studies on the role of these two kinds of cells during pregnancy were only localized on the recurrent spontaneous abortion, while literatures about the relationship between the Th17/Treg balance and preeclampsia were still limited. Through a comparative study on the expressions of the Th17 cells, Treg cells and related cytokines in peripheral blood samples of preeclampsia patients, healthy late-prengnant women and healthy non-pregnant women, this paper aims to probe into the role of immune responses mediated by Th17 and Treg cells in the pathogenesis of preeclampsia, and to provide clues for futher exploring of the mechanism of the disease.Methods A total of 25 preeclampsia patients and 27 healthy late-pregnant women who underwent routine antenatal examinations in Qilu hospital, Shandong University and 20 healthy non-pregant women were inrolled in this study. Blood from median cubital vein which was sampled prior to the treatment was anticoagulated by heparin sodium, and was respectively marked as pre-eclampsia group, normal pregnant group and non-pregnant group. We examined and compared the frequencies of IL-17-producing CD4+T cells as Th17 and CD4+ CD25+Foxp3+Treg cells which were expressed as a percentage of the total CD4+T cells and also the Th17/Treg ratio in peripheral blood samples of three groups by Flow cytometric, and the expressions of of IL-17, IL-10, and TGF-β1 in serum by Enzyme linked immunosorbent assay (ELISA).Results (1) Compared to both non-pregnant and normal pregnant group, the percentage of IL-17-producing CD4+T cells as Th17 in the total CD4+T cells in peripheral blood samples of the pre-eclampsia group was significantly increased (2.20±0.55% vs1.46±1.00%, P<0.01; 2.20±0.55% vs 0.95±0.48%, P<0.01); and the frequency of Th17 cell in normal pregnant group was significantly decreased than in non-pregnant women (0.95±0.48% vs 1.46±1.00%, P<0.01).(2) Compared to both non-pregnant and pre-eclampsia group, the percentage of CD4+CD25+Foxp3+Treg cell in the total CD4+T cells was strikingly increased in normal pregnant group (5.49±0.17% vs 4.80±0.13%, P<0.05; 5.49±0.17% vs 3.90±0.56%, P<0.01); while the prevalence of Treg cell in peripheral blood samples of the pre-eclampsia group was notably decreased compared with the non-pregnant group (3.90±0.56% vs 4.80±0.13%, P<0.01).(3) Compared to both non-pregnant and normal pregnant group, the Th17/Treg ratio in pre-eclampsia patients was impressively elevated (0.57±0.10 vs 0.31±0.10, P<0.01; 0.57±0.10 vs 0.18±0.73, P<0.01); the ratio in healthy late-pregnant women was notably lower than in non-pregnant women (0.18±0.73 vs 0.31±0.10, P<0.01).(4) Compared to both non-pregnant and normal pregnant group, the expressions of IL-17 and TGF-β1 were evidently higher in pre-eclampsia group (P<0.05), while the expression of IL-10 in blood simples of the normal pregnant group was imperceptibly increased (P>0.05); and there were slight detectable changes in the concentrations of IL-17 and TGF-β1 in normal pregnant group when compared with the non-pregnant group.Conclusion A successful pregnancy depends on the maternal humoral immune-tolerant status mediated by Treg cells. There is a shift in the Th17/Treg balance favouring skewness towards a pro-inflammatory status in preeclampsia, and the imbalance of Th17/Treg may be involved in the development and progression of preeclampsia. |
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