IMMUNOLOGICAL RESEARCH ON THE PATHOGENESIS OF PREECLAMPSIA AND THE PREDICTION OF ITS MANIFESTATION.

我们研究了子痫前期发病机制与人类白细胞抗原(HLA)-G之间的关系，HLA -G被认为在维持妊娠中起重要作用。首先，我们建立了酶联免疫吸附测定（ELISA）系统来测定可溶性HLA-G蛋白（参考文献1）。其次，针对子痫前期胎盘中滋养细胞中HLA-G的表达减弱和蜕膜组织中白细胞介素(IL)-2的异常表达，我们分析了在添加IL-2和不添加IL-2的培养条件下，HLA-G阴性和阳性滋养细胞的生长情况。我们发现滋养细胞系上HLA-G的表达完全消除了IL-2的生长抑制作用，这可能与妊娠期间母体对胎儿的耐受性及其紊乱有关，如先兆子痫（Ref 2）。第三，我们发现与HLA-G接触后，单核细胞中释放的T辅助1 （Th1）细胞因子的数量减少，单核细胞和外周血单核透明细胞（PBMCs）释放的T辅助2 （Th2）细胞因子的数量增加，而单核细胞中释放的Th2细胞因子的数量保持不变（文献3）。我们随后研究了复发性流产的发病机制及其使用父系单核细胞的免疫治疗机制，因为除了子痫前期，胎儿-母体免疫反应的紊乱被认为在复发性流产的发病机制中起重要作用。首先，我们发现HLA-G等位基因异常在复发性流产的发病机制中似乎没有什么影响（参考文献4）。其次，对复发性流产的免疫治疗不影响自然杀伤（NK）受体的表达，无论随后的妊娠结果如何，这表明复发性流产可能通过与NK受体状态改变无关的机制受益于免疫治疗（Ref 5）。第三，为了深入了解中药治疗复发性流产的实证依据，我们研究了Toki和saiei -to是否调节PBMCs中Th1和Th2细胞因子的释放。Toki和Sai增加了Th1细胞因子的释放，这可能具有治疗潜力，特别是在自身免疫相关的复发性流产中，Th2反应在病理上增强（参考文献6,7）。少

We have investigated the relationship between the pathogenesis of preeclampsia and human leukocyte antigen (HLA)-G which is thought to play an important role in maintaining pregnancy. First, we have established and enzyme-linked immunosorbent assay (ELISA) system to measure soluble HLA-G protein (Ref 1). Secondly, in regard to the fact that the expression of HLA-G on trophoblasts is attenuated and interleukin (IL)-2 is aberrantly expressed in decidual tissue in preeclamtic placenta, we analyzed the growth of HLA-G-negative and -positive trophoblast cell line in the culture with or without IL-2 supplementation. We found that the expression of HLA-G on trophoblastic cell line completely eliminated the growth-inhibitory effect of IL-2, which might be relevant to maternal tolerance of the fetus during pregnancy and its derangement as exemplified by preeclampsia (Ref 2). Thirdly, we found that upon the contact with HLA-G, the amounts of T helper 1 (Th1) cytokines released from decidual mono … More nuclear cells and peripheral blood monon clear cells (PBMCs) were decreased, while the amounts of T helper 2 (Th2) cytokine from PBMCs was increased with Th2 cytokine release from decidual mononuclear cells being unchanged (Ref 3).We then investigated the pathogenesis of recurrent abortion and the mechanism of its immunotherapy using paternal mononuclear cells because as well as preeclampsia, the derangement of feto-maternal immune reaction is thought to play an important role in the pathogenesis of recurrent abortion. First, we found that HLA-G allelic abnormality seemed to have little, if any, implication in the pathogenesis of recurrent abortion (Ref 4). Secondly, the immunotherapy for recurrent aborters did not affect the expression of natural killer (NK) receptors regardless of the outcome of subsequent pregnancies, suggesting that recurrent aborters may benefit from the immunotherapy through mechanisms unrelated to alteration in NK receptor status (Ref 5). Thirdly, to gent insight into the basis for the empirical usage of herbal medicines in the treatment of recurrent abortion, we examined whether Tokishakuyaku-san (Toki) and Sairei-to (Sai) modulate Th1 and Th2 cytokine release from PBMCs. Toki and Sai increased the release of Th1 cytokines, which may have therapeutic potential particularly in autoimmunity -related recurrent abortion where Th2 response is pathologically enhanced (Ref 6,7). Less