Immunological role of HLA-G for maintaining pregnancy

1. HLA-G多态性。我们发现了一个新的HLA-G等位基因，与之前报道的等位基因相比，它在外显子3上具有非同义的单碱基替换，并被WHO命名委员会正式命名为G**0104。G**0104在日本人群中最为常见。此外，我们在G**01012序列的外显子2中发现了一个单碱基错误并进行了纠正2。HLA-G和子痫前期。所有子痫前期患者胎盘外滋养细胞HLA-G蛋白表达均减弱。这些滋养细胞都含有IL-2，这在正常胎盘中是不存在的。此外，妊娠28周后发生子痫前期的妇女在妊娠前三个月的血清IL-2浓度高于正常孕妇。子痫前期胎盘中的IL-2可能通过诱导蜕膜淋巴细胞中淋巴因子激活的杀伤细胞来减少滋养细胞产生的血管生成物质，这可能与胎盘血管紊乱有关，这是子痫前期的特征性组织学特征。单核细胞的细胞因子释放和靶细胞上的HLA-G。单核细胞，如果与表达hla - g的细胞一起培养，可以增加其释放IL-3的能力，IL-3促进滋养层细胞的生长和发育，并降低抑制滋养层细胞生长的tnf - α。淋巴细胞上的自然杀伤受体。淋巴细胞在滋养细胞上表达可识别HLA-G的自然杀伤受体。

1. Polymorphism of HLA-G.We discovered a new allele of HLA-G which possessed a non-synonymous singlebase substitution in exon 3 compared with the previously reported alleles and was officially designated G**0104 by the WHO Nomenclature Committee. G**0104 was most common in Japanese population. In addition, we identified a single-base error in exon 2 in the sequence of G**01012 and corrected it.2. HLA-G and preeclampsia.The expression of HLA-G protein on the extravillous trophoblasts in placenta was attenuated in all the preeclamptic patients. All of these trophoblasts possessd IL-2 which was not observed in normal placenta. Further, serum concentrations of IL-2 in the first trimester of pregnancy in women who had preeclampsia develop after 28 weeks of pregnancy were higher than those of normal pregnant women. IL-2 in preeclamptic placenta might reduce the angiogenic substances arising from trophoblasts by inducing lymphokine activated killer cells from decidual lymphocytes, which might be relevant to deranged vasculature of the placenta, a characteristic histology in preeclampsia.3. Cytokine release from mononuclear cells and HLA-G on the target cells.Mononuclear cells, if cultured with HLA-G-expressing cells, increase their ability to release IL-3 which enhances the growth and development of trophoblasts and decrease TNF-alpha which suppresses the growth of trophoblasts.4. Natural killer receptor on the decidual lymphocytes.Decidual lymphocytes express the natural killer receptors which recognize HLA-G on the trophoblasts.