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1990 Fiscal Year Final Research Report Summary

Analysis of the Mechanism of Induction of T cell development in the Thymus.

Research Project

Project/Area Number 01480189
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionKyoto University

Principal Investigator

YOSHIMOTO Katsura  Kyoto Univ., Chest Dis. Res. Inst., Professor, 胸部疾患研究所 (90027095)

Co-Investigator(Kenkyū-buntansha) FUJIMOTO Shinji  Kyoto Univ., Chest Dis. Res. Inst. Assistant Prof., 胸部疾患研究所, 助手 (60199370)
KINA Tatsuo  Kyoto Univ., Chest Dis. Res. Inst. Associate Prof., 胸部疾患研究所, 助教授 (30127071)
Project Period (FY) 1989 – 1990
KeywordsThymus / T cell / Development / Stroma cells / Cytokine
Research Abstract

This project aimed at investigating the mechanism of T cell differentiation and growth in the thymus, and the following points were clarified.
1. The most immature pre T cells in the thymus. The precursor activity of various subpopulations of thymus cells were investigated by transferring into deoxyguanosine (dGuo)-treated Fetal Thymus Organ Culture (FTOC) by micro i. T. Method (cell injection method with a microinjector). It was found that the pre T cells in thymic Thy-1^- cells were the most immature among those ever discovered, and it was suggested that they were the immediate progeny of the stem cells immigrated from the bone marrow.
2. Importance of macrophages (MUphi) in T cell growth. With micro i. T. Transfer system, it was shown that MUphi promoted the differentiation and/or growth of T cells in dGuo-FTOC. Dendritic cells (DC) were unable to play a similar role.
3. Binding of T lineage cells on the surface of stromal cells. We have succeeded in isolating a new cell surface molecule (107KDa glicoprotein) that mediates the binding between thymic fibroblastoid stromal cell lines and an immature T cell line. Using a monoclonal antibody to this molecule, studies are in progress to clarify the role of cell to cell interaction on T cell development.
4. Thymic stromal cell line and cytokines. A fibroblastoid stromal cell line TSt-4 derived from murine fetal thymus is able to support the growth of CD4^+ helper T cells from CD4^-8^- cells. Although TSt-4 synthesizes IL-7 and M-CSF, these cytokines themselves seemed unable to support the differentiation of CD4^+ T cells, suggesting the importance of cell to cell interaction or unknown factors.
5. Requirement of DC in intrathymic tolerance. Cells required for clonal deletion type tolerance to a superantigen Mls-1^a was investigated in micro i. T. System. It was found that DC and B cells were required. B cells played only to supply the Mls antigen, whereas DC were strongly suggested to be the effector cells.

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Kina,T.: "Identification of a 107KDa glycoprotein that mediates adhesion between stromal cells and Hematolymphoid cells." J.Exp.Med.173. 372-381 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mazda,O.: "Requirement of dendritic clls and B cells in the clonal deletion of Mlsーreactive T cells in the thymus." J.Exp.Med.173. 539-547 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Gyotoku,J.: "Inhibition of human immunodeficiency virus replication in a human T cell line by antisense RNA expressed in the cell." Virus genes,in press.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwai,K.: "Qualitative difference of antiーDNA antibodyーproducing cell precursors in teh preimmune B cell repertoire between normal and lupusーprone mice." Clinical Exp.Med.,in press.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桂 義元: "胸腺ストロ-マ細胞株上でのT細胞分化" 代謝,増刊号(免疫 '90). 27. 187-195 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桂 義元: "T細胞の初期分化と胸腺ストロ-マ細胞" 血液・腫瘍科. 21. 233-243 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桂 義元 (共著): "岩波書店." 岩波講座ー分子生物科学11 「生命体のまもり方」. (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kina, T.: "Identification of a 107KDa glycoprotein that mediates adhesion between stromal cells and hematolymphoid cells." J. Exp. Med.173. 373-381 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mazda, O.: "Requirement of dendritic cells and B cells in the clonal deletion of Mls-reactive T cells in the thymus." J. Exp. Med.173. 539-547 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Gyotoku, J.: "Inhibition of human immunodeficiency virus replication in a human T cell line by antigens RNA expressed in the cell." Virus Genes.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwai, K.: "Qualitative difference of anti-DNA antibody-producing cell precursors in the preimmune B cell repertoire between normal and lupus-prone mice." Clinical Exp. Med.

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-08-12  

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