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Immunological role of HLA-G for maintaining pregnancy

Research Project

Project/Area Number 07671768
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionUniversity of Tokyo

Principal Investigator

FUJII Tomoyuki  University of Tokyo, Hospital, Assistant Professor, 医学部・附属病院, 講師 (40209010)

Co-Investigator(Kenkyū-buntansha) 前島 正基  東京大学, 医学部(病), 助手 (10251307)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
KeywordsHLA-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
Research Abstract

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.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamashita, T et al: "Correction of the HLA-G^*01012 genomic sequence" Tissue Antigens. 49. 673-674 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hara, N et al: "Altered expression of human leukocyte antigen G(HLA-G)on extravillous trophoblasts in preeclampsia." Am.J.Reprod.Immunol.36. 349-358 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hamai, Y et al: "Evidence for basic fibroblast growth factor as a crucial angiogenic growth factor,released from human trophoblasts during early gestation." Placenta. (印刷中). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hamai, Y et al: "Pathogenetical implication of interleukin-2 expressed in preeclamptic decidual tissues." Am J Reprod Immunol. 38. 83-88 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Maejima, M et al: "Presence of HLA-G expressing cells modulates the ablity of peripheral blood mononuclear cells to release cytokines." Am J Reprod Immunol. 38. 79-82 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hara, N, Fujii, T, Yamashita, T, et al: "Histochemical demonstration of interleukin-2 in decidua cells of patients with preeclampsia." Am J Reprod Immunol. 34. 44-51 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hamai, Y, Fujii, T, Yamashita, T, et al: "Evidence for an elevation in serum interleukin-2 and tumor necrosis factor-α levels before the dinical manifestations" Am J Reprod Immunol. 38. 89-93 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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 polymorphism(SSCP)method." Am J reprod Immuuol. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamashita T,Fujii T,Watanabe Y,et al.: "HLA-G gene polymorphism in a Japanese population." Immunogenetics. 44. 186-191 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamashita T,Fujii T,Tokunaga K,et al.: "Correction of the HLA-G^*01012 genomic sequence." Tissue Antigens. 49. 673-674 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hara N,Fujii T,Yamashita T,et al.: "Altered expression of human leukocyte antigen G (HLA-G) on extraillous trophoblasts in preeclampsia : Immunohistochemical demonstration with anti-HLA-G specific antibody '87G' and anti-cytokeratin antibody 'CAM5.2' ." Am J Reprod Immunol. 36. 349-358 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hara N,Fujii T,Okai T,et al.: "Histochemical demonstration of interleukin-2 in decidua cells of patients with preeclampsia." Am J Reprod Immunol. 34. 44-51 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hamai Y,Fujii T,Yamashita T,et al.: "Evidence for basic fibroblast growth factor as a crucial angiogenic growth factor, released from human trophoblasts during early gestation." Placenta. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hamai Y,Fujii T,Yamashita T,et al.: "Pathogenetical implication of interleukin-2 expressed in preeclamptic decidual tissues : A possible mechanism of deranged vasculature of the placenta associated with preeclampsia." Am J Reprod Immunol. 38. 83-88 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hamai Y,Fujii T,Yamashita T,et al.: "Evidence for an elecation in serum interleukin-2 and fumor necrosis factor-alpha levels before the clinical manifestations of preeclampsia." Am J Reprod Immunol. 38. 89-93 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Maejima M,Fujii T,Kozuma S,et al.: "Presence of HLA-G expressing cells modulates the ability of peripheral blood mononuclear cells to release cytokines." Am J Reprod Immunol. 38. 79-82 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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 polymorphism (SSCP) method." Am J reprod Immunol. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamashita T et al: "HLA-G gene polymorphism in Japanese population" Immunogenetics. 44. 186-191 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamashita T et al: "Correction of the HLA-G^*01012 genomic sequence." Tissue Antigens. 49. 673-674 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hara N et al: "Altered expression of human leukocyte antigen G(HLA-G)on extravillous trophoblasts in preeclampsia." Am.J.Reprod.Immunol.36. 349-358 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hamai Y et al: "Evidence for basic fibroblast growth factor as a crucial angiogenic growth factor,released from human trophoblasts during early gestation." Placenta. 印刷中. (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hamai Y et al: "Pathogenetical implication of interleukin-2 expressed in preeclamptic decidual tissues." Am.J.Reprod.Immunol.38. 83-88 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Maejima M et al: "Presence of HLA-G expressing cells modulates the ability of peripheral blood mononuclear cells to release cytokines." Am.J.Reprod.Immunol.38. 79-82 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hara N.,Fujii T.,Yamashita T.,Kozuma S.,Okai T.,Taketani Y: "Altered expression of human leukocyte antigen G(HLA-G)on extavillous trophoblasts in preeclampsia." Am.J.Reprod.Immunol.36. 349-358 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamashita T.,Fujii T.,Watanabe Y.,Tokunaga K.,Taketani Y: "HLA-G gene polymorphism in Japanese population." Immunogenetics. 44. 186-191 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujii T.,Tsusima R.,Okai T.,Shibata T.,Taketani Y: "Allo-nonspecific elevation of maternal killer cell activity in intrauterime growth restriction." International J.Gynecol.Obstet. 52. 237-242 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ryo E.,Fujii T.,Tsutsumi O.,Okai T.,Taketani Y: "Isolated ‘contrdctions' of the uterine cervix in a patient with incomptetent cervix." International J.Gynecol.Obstet. 53. 51-53 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 藤井 知行: "不育症" 医学のあゆみ. 別刷. 29-31 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 藤井 知行: "子宮内胎児発育遅延(IUGR)と自己免疫異常" 産婦人科の実際. 45. 1443-1445 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tomoyuki Fujii: "Histochemical Demonstration of Interleukin-2 in Decidua Cells of Patients with preeclampsia" American Journal of Reproductive Immunology. 34. 44-51 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tomoyuki Fujii: "Allo-non-specific elevation of maternal killer cell activity in intrauterine growth restriction" International Journal Gynecology & Obstetrics. (印刷中). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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