Immunological role of HLA-G for maintaining pregnancy

HLA-G 对维持妊娠的免疫学作用

• 批准号: 07671768
• 负责人: FUJII Tomoyuki
• 金额: $ 1.6万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671768/
• 关键词: HLA-G; pregnancy; Immunology; preeclampsia; cytokine; Natural Killer Receptor; Trophoblast; ナチュラルキラーレセプター; HLA; 胎盤; インターロイキン-2; 血管増殖因子; キラー細胞; 免疫組織化学染色

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.

1. HLA-G的多态性：我们发现了一个新的HLA-G等位基因，与以前报道的等位基因相比，该等位基因在第3外显子有一个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，我们还发现了G**01012基因外显子2的一个单碱基错误，并进行了纠正.子痫前期患者胎盘绒毛外滋养细胞HLA-G蛋白表达减弱。这些滋养细胞均含有IL-2，而正常胎盘中则无此现象。此外，在妊娠28周后发生先兆子痫的妇女中，妊娠早期的血清IL-2浓度高于正常妊娠妇女。先兆子痫胎盘中的IL-2可能通过诱导来自蜕膜淋巴细胞的淋巴因子激活的杀伤细胞来减少滋养层产生的血管生成物质，这可能与胎盘血管系统紊乱有关，这是先兆子痫的特征性组织学。3.单核细胞释放的细胞因子和靶细胞上的HLA-G，单核细胞与表达HLA-G的细胞共同培养，增加其释放IL-3的能力，从而促进滋养层细胞的生长和发育，并降低TNF-α，从而抑制滋养层细胞的生长.蜕膜淋巴细胞上的自然杀伤受体：蜕膜淋巴细胞表达识别滋养层细胞上HLA-G的自然杀伤受体。

项目成果

Yamashita, T et al: "Correction of the HLA-G^*01012 genomic sequence" Tissue Antigens. 49. 673-674 (1997)

Yamashita, T 等人：“HLA-G^*01012 基因组序列的校正”组织抗原。

Miki, A, Ishikawa, Y, Yabe, T, Furukawa, H, Fujii, T, Tokunaga, K, et al: "Human lymphocytes obtained from decidual tissue express killer activatory receptors(KARs)as well as killer inhibitory receptors(KIRs)Analysis using a single strand conformation pol

Miki, A, Ishikawa, Y, Yabe, T, Furukawa, H, Fujii, T, Tokunaga, K, et al：“从蜕膜组织中获得的人类淋巴细胞表达杀伤激活受体 (KAR) 以及杀伤抑制受体 (KIR)

Yamashita, T et al.: "HLA-G gene polymorphism in Japanese population" Immunogenetics. 44. 186-191 (1996)

Yamashita, T 等人：“日本人群中的 HLA-G 基因多态性”免疫遗传学。

Miki A,Ishikawa Y,Yabe T,Furukawa H,Fujii T,Tokunaga K,et al.: "Human lymphocytes obtained from decidual tissue express killer activatory receptors (KARs) as well as killer inhibitory receptors (KIRs) ; Analysis using a single strand conformation polymorp

Miki A、Ishikawa Y、Yabe T、Furukawa H、Fujii T、Tokunaga K 等人：“从蜕膜组织中获得的人类淋巴细胞表达杀伤激活受体 (KAR) 以及杀伤抑制受体 (KIR)；使用单个细胞进行分析

Hamai Y et al: "Pathogenetical implication of interleukin-2 expressed in preeclamptic decidual tissues." Am.J.Reprod.Immunol.38. 83-88 (1997)

Hamai Y 等人：“先兆子痫蜕膜组织中表达的白细胞介素 2 的病理遗传学意义。”