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

辅助性T（Th）细胞在调节免疫应答中起核心作用。本文从Th 1/Th 2/Th 17和调节性T细胞（Treg）的角度探讨不明原因反复流产、早产和子痫前期的病理生理机制。我们已经报道了Treg细胞在妊娠早期对同种异体妊娠的维持起着至关重要的作用，但在妊娠晚期则没有。我们还发现，父亲抗原特异性Treg细胞在植入前的子宫引流淋巴结和植入后的子宫中增加。我们已经发现NKreg细胞在妊娠子宫中增加，并且它们在其表面上表达CD 25。它们产生免疫抑制细胞因子，如IL-10和TGFβ。Th 17细胞在早产合并重度绒毛膜炎患者和晚期自然流产患者子宫内均增高，且与中性粒细胞数呈显著正相关。IL-17还以剂量依赖性方式增加TNF-α诱导的羊膜间充质细胞分泌IL-8。在先兆子痫中，我们发现由外周血T细胞和NK细胞产生的VEGF和半乳糖凝集素-1减少，表明血管生成和耐受诱导系统在先兆子痫中失调。

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.