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Artificial thymus-a completely re-organized thymic tissue with stromal cell lines of defined origins

Research Project

Project/Area Number 07670360
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

IWABUCHI Kazuya  Hokkaido Univ., Inst.Immunol.Sci., Inst., 免疫科学研究所, 助手 (20184898)

Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsthymus / artificial thymus / stromal cells / cell transplantation / monoclonal antibody
Research Abstract

During my term of project, following results were obtained.
1) Thymic stromal cell lines were established from BALB/c and AKR/J strains of mice.
2) One of stromal cell lines from BALB/c strain expressed Thy 1 molecules. An inhibitory signal for growth was shown to be transduced from Thy 1 molecules.
3) Some of stromal cell lines were shown to express Src-family protein tyrosine kinases, such as Src and Fgr. And medullary stromal cells were positive for Fgr proteins by immunohistology with anti-Fgr mAb, 2H2 which was established in our laboratory. (Microbiol.Immunol.40 : 223,1996.)
4) Selective activation for effector functions of DB14 T-cell clone was exhibited when an antigenic peptide was presented with thymic cortical and medullary epithelial cell lines (ibid.41 : 51,1997).
5) Fifteen mAbs were established against stromal cells of AKR/J origin. Four clones of hydridoma were established with limiting dilution method. With mAbs, HI-C,HI-M,HI-E,and HI-F,tissue and strain distributions were … More analyzed.
6) Stromal cells were cultured in 3-dimension in gel or on highly porous beads for in vivo transfer. Among materials tested, gelatin-based porous beads (Cultispher^<TM>, Percell Biolytica) and fibrin clot in combination with gelatin beads could be candidates for biocompatible carriers for transfer or transplantation of re-organized stromal cells, or artificial thymus. Biocompatibility, especially on adhesion between stromal cells and bead surface should be improved.
7) Transplanted stromal cells in gel under kidney capsule were observed as one to several layrs of stromal cells with an infiltration of mononuclear cells. These artificial thymi in situ did not seem to function as thymic tissues but induced inflammatory responses.
8) Re-organization of thymic tissue with stromal cells of defined origins should be performed without any loss of certain types of stromal cells, since negative selection seemed perturbed in the thymus of aly/aly (alymphoplasia) mutant mouse that has a defect in medullary function due to a loss of a certain cell type or a molecule on certain cell (Proc.Natl.Acad.Sci.USA 94 : 2472,1997). Less

Report

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

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Arase-Fukushi Noriko: "Production of minor lymphocyte stimulatory-1^a antigens from T cell subsets." Immunobiol.193. 378-390 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 岩渕和也: "医学用語解説 ポジティブ/ネガティブセレクション" 炎症と免疫. 3. 100-101 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hatakeyama Shigetsugu: "Fgr expression restricted to subpopulation of monocyte/macrophage lineage in resting condition is induced in various hematopoietic cells after activation or transformation" Microbiol Immunol.40(3). 223-231 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Katoh Masahito: "A promiscuous T cell hybridoma restricted to various I-A molecules." Eur. J. Immunol.26. 976-980 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Itoh Yasushi: "Determination of the allele-specific antigen-binding site on I-A^k and I-A^b molecules." Eur. J. Immunol.26. 1314-1321 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kaneda Rika: "Detachment activity but not cytotoxicity induced in a T-cell clone following antigen presentation in the presence of thymic epithelial cells." Microbiol Immunol.41(1). 51-61 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakagawa Ken-ichi: "Generation of NK1. 1^+TCR α/β^+ thymocytes associated with intact thymic structure." Proc. Natl. Acad. Sci. USA. 94. 2472-2477 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwabuchi Kazuya: "Csk over-expression reduces productions of several monokines and nitric oxide but enhances PGE_2 production in response to LPS in a macrophage cell line, J774A. 1." Eur. J. Immunol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kaneda Rika: "Dissociation of Fas-mediated cytotoxicity and FasL expression in a cytotoxic CD4^+T cell clone." Immunol Lett.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Onoe Kazunori: "Influence of graft versus host reaction on the T cell repertoire differentiation from bone marrow precursors following allogeneic bone marrow transplantation." Transplant. Immunol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takayanagi Toshiaki: "Proceedings of International Symposium on Bone Marrow Transplantation (eds. Ikehara Susumu et al.)" Springer Verlag Tokyo, 331 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Arase-Fukushi Noriko: "Production of minor lymphocyte stimulatory-1^a antigens from T cell subsets." Immunobiol. 193. 378-390 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hatakeyama Shigetsugu: "Fgr expression restricted to subpopulation of monocyte/macrophage lineage in resting condition is induced in various hematopoietic cells after activation or transformation" Microbiol.Immunol.40 (3). 223-231 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Katoh Masahito: "A promiscuous T cell hydridoma restricted to various I-A molecules." Eur.J.Immunol.26. 976-980 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Itoh Yasushi: "Determination of the allele-specific antigen-binding site on I-A^k and I-A^b molecules." Eur.J.Immunol.26. 1314-1321 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kaneda Rika: "Detachment activity but not cytotoxicity induced in a T-cell clone following antigen presentation in the presence of thymic epithelial cells." Microbiol.Immunol.41 (1). 51-61 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakagawa Ken-ichi: "Generation of NK1.1^+TCRalpha/beta^+ thymocytes associated with intact thymic structure." Proc.Natl.Acad.Sci.USA. 94. 2472-2477 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kaneda Rika: "Dissociation of Fas-mediated cytotoxicity and FasL expression in a cytotoxic CD4^+ T cell clone." Immunol.Lett.55. 53-60 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Onoe Kazunori: "Influence of graft versus host reaction on the T cell repertoire differentiating from bone marrow precursors following allogeneic bone marrow transplantation." Transplant.Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwabuchi Kazuya: "Csk over-expression reduces productions of several monokines and nitric oxide but enhances PGE_2 production in response to LPS in a macrophage cell line, J774A.1." Eur.J.Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hatakeyama Shigetsugu: "Fgr expression restricted to subpopulation of monocyte/macrophage lineage in resting condition is induced in various hematopoietic cells after activation or transformation" Microbiol Immunol.40(3). 223-231 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Katoh Masahito: "A promiscuous T cell hybridoma restricted to various I-A molecules." Eur. J. Immunol.26. 976-980 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Itoh Yasushi: "Determination of the allele-specific antigen-binding site on I-A^k and I-A^b molecules." Eur. J. Immunol.26. 1314-1321 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kaneda Rika: "Detachment activity but not cytotoxicity induced in a T-cell clone following antigen presentation in the presence of thymic epithelial cells." Microbiol Immunol.41(1). 51-61 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Iwabuchi Kazuya: "Csk over-expression reduces productions of several monokines and nitric oxide but enhances PGE_2 production in response to LPS in a macrophage cell line, J774A. 1." Eur. J. Immunol.27(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakagawa Ken-ichi: "Generation of NK1.1+TCRα/β^+ thymocytes associated with intact thymic structure." Proc. Natl. Acad. Sci. USA. 94(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kaneda Rika: "Dissociation of Fas-mediated cytotoxicity and FasL expression in a cytotoxic CD4+T cell clone." Immunol. Lett.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Onoe Kazunori: "Influence of graft versus host reaction on the T cell repertoire differentiating from bone marrow precusors following allogeneic bone marrow transplantation" Transplant. Immunol.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takayanagi Toshiaki: "Proceedings of International Symposium on Bone Marrow Transplantation (eds. Ikehara Susumu et al.)" Springer Verlag Tokyo, 331 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hatakeyama Shigetsugu: "Fgr expression restricted to subpopulation of monocyte/macrophage lineage in resting conditions is induced in various hematopoietic cells after activation or transformation" Microbiol.Immunol.40(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Katoh Masahito: "Apromiscuous T cell hybridoma restricted to various I-A molecules." Eur.J.Immunol.26(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 岩渕 和也: "医学用語解説 ポジティブ/ネガティブセレクション" 炎症と免疫. 3. 100-101 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takayanagi Toshiaki: "Proceedings of International Symposium On Bone Marrow Transplantation(eds.Ikehara,S.et al.)" Springer Verlag,Tokyo(in press),

    • Related Report
      1995 Annual Research Report

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

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