Immunological role of HLA-G for maintaining pregnancy

1.人类白细胞抗原-G基因的多态性我们发现了一个新的等位基因，与已报道的等位基因相比，它在外显子3具有非同义的单碱基替换，被WHO命名委员会正式命名为G**0104。G**0104在日本人群中最常见。此外，我们还在G**01012序列的外显子2中发现了一个单碱基错误，并对其进行了纠正。所有子痫前期患者胎盘绒毛外滋养细胞上的人类白细胞抗原-G蛋白表达均减弱。这些滋养层细胞均具有正常胎盘中未见的IL-2。此外，妊娠28周后发生先兆子痫的妇女在妊娠早期的血清IL-2浓度高于正常孕妇。子痫前期胎盘组织中的IL-2可能通过诱导蜕膜淋巴细胞产生淋巴因子激活的杀伤细胞，从而减少滋养层细胞产生的血管生成物质，这可能与子痫前期胎盘血管紊乱有关。单个核细胞释放细胞因子，靶细胞释放人类白细胞抗原G，单核细胞与表达人类白细胞抗原G的细胞共同培养，增加其释放IL-3的能力，促进滋养层细胞的生长发育，降低抑制滋养层细胞生长的肿瘤坏死因子-α。蜕膜淋巴细胞上的自然杀伤受体。个别淋巴细胞表达自然杀伤受体，识别滋养细胞上的人类白细胞抗原-G。

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.