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2003 Fiscal Year Final Research Report Summary

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
KeywordsStromal cell / chemokine / cytokine / Lymphoid tissues / Dendritic cell / Organogenesis / Hybrid type artificial organ / Immunological device
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.

  • Research Products

    (14 results)

All Other

All Publications (14 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2005-04-19  

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