Pathophysiology of unexplained recurrent pregnancy loss, preterm labor and preeclampsia from the viewpoint of reproductive immunology

辅助性T细胞(Th)在调节免疫反应中起着核心作用。我们从新的Th1/Th2/Th17和调节性T(Treg)细胞范式的角度讨论了原因不明的反复妊娠丢失、早产和先兆子痫的病理生理学。我们已经报道，Treg细胞在妊娠早期对同种异体妊娠的维持起着重要作用，但在妊娠晚期不起作用。我们还发现，在植入前和植入后子宫引流淋巴结中，父系抗原特异性Treg细胞增加。我们发现NKreg细胞在怀孕的子宫中增加，它们在其表面表达CD25。它们产生免疫抑制细胞因子，如IL-10和转化生长因子β。早产重度绒毛膜羊膜炎和晚期自然流产患者子宫中Th17细胞数量增加，且Th17细胞数量与中性粒细胞数量呈正相关。IL-17还以剂量依赖的方式促进肿瘤坏死因子-α诱导的羊膜间充质细胞分泌IL-8。在子痫前期，我们发现外周血T细胞和NK细胞产生的血管内皮生长因子和Galectin-1减少，提示血管生成和耐受诱导系统在子痫前期中调节失调。

T-helper (Th) cells play a central role in modulating immune responses. We discuss the pathophysiology of unexplained recurrent pregnancy loss, preterm labor and preeclampsia from the viewpoint of new Th1/Th2/Th17 and regulatory T (Treg) cell paradigm. We have reported that Treg cells play an essential role for maintenance of allogeneic pregnancy in early pregnancy, but not in late pregnancy. We also found that paternal antigen-specific Treg cells increase in uterine draining lymphonodes before the implantation and in uterus after implantation. We have found NKreg cells increase in the pregnant uterus and they express CD25 on their surface. They produce immunosuppressive cytokines such as IL-10 and TGFβ. Th17 cells increased in the uterus of preterm labor cases with severe chorioamnionitis and of spontaneous abortion cases in late stage, and there were significant positive correlation between Th17 cells number and neutrophil number. IL-17 also augment the TNF-α-induced IL-8 secretion by amniotic mesenchymal cells in a dose dependent manner. In preeclampsia, we found the production of VEGF and Galectin-1 by peripheral blood-T cells and -NK cells was decreased suggesting that angiogenesis and tolerance induction systems are dysregulated in preeclampsia.