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Generation of artificial lymphoid tissues and their application.

Research Project

Project/Area Number 13557025
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Immunology
Research InstitutionKyushu University

Principal Investigator

WATANABE Takeshi  Kyushu University, Medical Institute of Bioregulation, Molecular Immunology, MD, Prof., 生体防御医学研究所, 教授 (40028684)

Co-Investigator(Kenkyū-buntansha) SUEMATSU Sachiko  Kyushu University, Medical Institute of Bioregulation, Cellular Immunology, MD, Assit., 生体防御医学研究所, 助手 (50250345)
MATSUDA Takehisa  Kyushu University, Graduate School of Medicine, Tissue Engineering, MD, Prof., 医学研究院, 教授 (60142189)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2003: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥6,100,000 (Direct Cost: ¥6,100,000)
KeywordsStromal cell / chemokine / cytokine / Lymphoid tissues / Dendritic cell / Organogenesis / Hybrid type artificial organ / Immunological device / 人工リンパ節 / 生体適合性高分子材料 / ケモカイン / 三次元構造骨格 / 移植 / 人工リンパ組織 / 組織工学 / 免疫不全症の治療 / 重傷感染症の治療 / 腫瘍免疫
Research Abstract

We showed that our artificial lymphoid tissues possess not only basic structure of normal lymphoid tissue, but also immunologically important function of antigen specific antibody production. To construct "artificial lymphoid tissue" structures, a certain biocompatible material containing a thymus derived stromal cell line and cytokines was prepared, and transplanted to renal subcapsular space in mice. The accumulation of the lymphocytes was accelerated by the addition of bone marrow derived mature dendritic cells(DCs) in the graft along with the stromal cells at the time of transplantation.
Many and relatively large T cell foci surrounded by B cell accumulation, which is similar to T cell and B cell area in secondary lymphoid tissues. Further immunohistochemical analysis revealed that the grafts with many T cell and B cell accumulation structurally resembled secondary lymphoid tissues in following aspects(points) ; 1)CD11c+ dendritic cells were found scattered both in T cell and B cell accumulation in the graft, 2)the CD4/CD8 ratio of T cells in the cluster was similar to that of T cell areas in normal lymph node tissues, 3)some of B cell clusters contained CR1 positive dendritic cells in the center, suggesting follicular dendritic network formation, 4)peanut agglutinin(PNA) positive B cells were detected in some of B cell clusters, 5)Syndecan-1 positive plasma cells were found around B cell accumulation, and 6)PNAd(peripheral node addressin) or MAdCAM-1(mucosal addressin cell adhesion molecule-1) positive HEV(high endothelial venule)-like structure was found in some of the grafts(especially) with many T cell and B cell accumulation.
In addition, antigen specific antibody formation in the grafts was confirmed by enzyme-linked immunospot(ELISPOT) assay and immunohistochemical analysis.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] K.Oya: "Appearance of the LAT protein at an early stage of B-cell development and its possible role."Immunology. 109. 351-359 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] B.Jones: "Hematopoietic stimulation by a dipeptidyl peptidase inhibitor reveals a novel regulatory mechanism and therapeutic treatment for blood cell deficiencies."Blood. 102(5). 1641-1648 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.F.Gao: "Analysis of the role of Bphs/Htrh1 in the genetic control of responsiveness to pertussis toxin."Infection and Immunity. 71. 1281-1287 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] R.Bahar: "Growth retardation, Polyploidy and multinucleation induced by Clast3,a novel cell cycle-regulated protein."J.Biol.Chem. 277. 40012-40019 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Yuasa: "Lyn is essential for Fcγ receptor III-mediated systemic anaphylaxis but not for the Arthus reaction."J.Exp.Med.. 193(5). 563-571 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Oya: "Appearance of the LAT protein at an early stage of B-cell development and its possible role."Immunology. 109. 351-359 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Umeda: "In vitro cooperation between Bcl-xL and the phophoinositide 3-kinase-Akt signaling pathway for the protection of epidermal keratinocytes from apoptosis."The FASEB Journal. 17. 610-620 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.F.Gao: "Analysis of the role of Bphs/Htrh1 in the genetic control of responsiveness to pertussis toxin."Infection and Immunity. 71. 1281-1287 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] D.Himeji: "Characterization of caspase-8L : a novel isoform of caspase-8 that behaves as an inhibitor of the caspase cascade."Blood. 99. 4070-4078 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Jutel: "Immune regulation by histamine."Current Opinion in Immunology. 14. 735-740 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] R.Z.Ma: "Identification of Bphs, an autoimmune disease locus, as histamine receptor H1."Science. 297. 620-623 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] R.Bahar: "Growth retardation, polyploidy and multinucleation induced by Clast3, a novel cell cycle-regulated protein."J.Biol.Chem. 277. 40012-40019 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Jutel: "Histamine regulates T cell and antibody responses by differential expression of H1 and H2 receptors."Nature. 413. 420-425 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Z-Li Huang: "Arousal effect of orexin A depends on activation of the histaminergic system."Proc.Natl.Acad.Sci.USA. 98. 9965-9970 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Oya: "Appearance of the LAT protein at an early stage of B-cell development and its possible role."Immunology. 109. 351-359 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] B.Jones: "Hematopoietic stimulation by a dipeptidyl peptidase inhibitor reveals a novel regulatory mechanism and therapeutic treatment for blood cell deficiencies."Blood. (in press). (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] J.F.Gao: "Analysis of the role of Bphs/Htrh1 in the genetic control of responsiveness to pertussis toxin."Infection and Immunity. 71. 1281-1287 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] R.Bahar: "Growth retardation, polyploidy and multinucleation induced by Clast3, a novel cell cycle-regulated protein."J.Biol.Chem. 277. 40012-40019 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Yuasa: "Lyn is essential for Feγ receptor III-mediated systemic anaphylaxis but not for the Arthus reaction."J.Exp.Med.. 193(5). 563-571 (2001)

    • Related Report
      2003 Annual Research Report
  • [Publications] D.Himeji: "Caracterization of caspase-8L : a novel isoform of caspase-8 that behaves as an inhibitor of the caspase cascade"Blood. 99. 4070-4078 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] R.Z.Ma: "Identification of Bphs, an autoimmune disease locus, as histamine receptor H1"Science. 297. 620-623 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] R.Bahar: "Growth retardation, polyploidy and multinucleation induced by Clast3, a novel cell cycle-regulated protein"J. Biol. Chem. 277. 40012-40019 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Jutel: "Immune regulation by histamine"Current Opinion in Immunology. 14. 735-740 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Oizumi: "RCAS1 expression, A potential prognostic marker for adenocarcinomas of the lung"Oncology. 62. 333-339 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Izushi: "The role of histamine H1 receptors in late phase reaction of allergic conjunctivitis"Eur. J. Pharmacology. 440. 79-82 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Jutel: "Histamine regulates T cell and antibody responses by differential expression of H1 and H2 receptors"Nature. 413. 420-425 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Z-Li Huang: "Arousal effect of orexin A depends on activation of the histaminergic system"Proc. Natl. Acad. Sci. USA. 98. 9965-9970 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Izumi: "Expression of tumor associated antigen RCAS1 is significantly correlated with poor prognosis in non small cell lung cancer"Cancer. 92(2). 446-451 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Oshima: "Expression of human tumor-associated antigen RCAS1 in Reed-Sternberg cells in association with Epstein-Barr virus infection. A potential mechanism of immune evasion"Int. j. Cancer. 93. 91-96 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Yuasa: "Lyn is essential for Fcγ receptor III-mediated systemic anaphylaxis but not for the Arthus reaction"J. Exp. Med. 193(5). 563-571 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Matsushima: "RCAS1: A novel regulator of apoptosis of erythroid progenitor cells"Blood. 96. 313-321 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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