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Elucidation of the mechanism of lineage commitment and differentiation in T cell development

Research Project

Project/Area Number 11470086
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

KATSURA Yoshimoto  Institute for Frontier Medical Science, Kyoto Univ., Professor, 再生医科学研究所, 教授 (90027095)

Co-Investigator(Kenkyū-buntansha) FUJIMOTO Shinji  Institute for Frontier Medical Science, Kyoto Univ., Assist. Prof., 再生医科学研究所, 助手 (60199370)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2001: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2000: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1999: ¥6,000,000 (Direct Cost: ¥6,000,000)
KeywordsT cell / NK cell / differentiation / thymus / progenitor
Research Abstract

In our previous studies, we have shown that T cell progenitors (p-T) are produced in fetal liver from the hematopoietic stem cell (HSC) through the stage of p-MT that is capable of generating myeloid and T cells. It was unclear, however, whether the p-MT are directly produced from the HSC or through an undetermined intermediate stage. In the present study, we newly developed the MLP<METB> that is assay capable of determining the developmental potential of individual progenitors towards myeloid, erythroid, T and B cell lineages. With this assay, we identified the p-MTB, the common progenitor for p-MT and PMB. P-METB (HSC) and p-ME were also identified. We have previously shown that prethymic p-T as well as the earliest thymic p-T retain NK potential. In the present study, we showed that these p-T/NK also retain DC potential. The developmental potential of p-T/NK/DC were found to be sequentially restricted to T cell lineages in the thymus during the progression of stages from CD44+CD25" to CD44 CD25+. By introducing the Id2 gene into the p-T/NK/DC with a retroviral vector, generation of αβT cells but not γδT cells was completely arrested.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Ohmura, K. et al.: "Immature multipotent hematopoietic progenitors lacking long-term bone marrrow-reconstituting activity in the aorta-gonad-mesonephros region of murine day 10 fetuses"Journal of Immunology. 166. 3290-3296 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ikawa, T. et al.: "Commitment to natural killer clels requires the helix-loop-helix inhitibor Id2"Proc. Natl. Acad. Sci. USA. 98. 5164-5169 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsura, Y. et al.: "Stepwise lineage restriction of progenitors in lympho-myelopoiesis"International Review of Immunology. 20. 1-20 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Egawa, T. et al.: "The earliest stages of B cell development require a chemokine stormal cell-derived factor/pre-B cell growth-stimulating factor"Immunity. 15. 1-20 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoi, M. et al.: "Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage"International Immunology. 13. 1203-1211 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsura, Y.: "Redefiniation of lymphoid progenitors"Nature Reviews Immunology. 2. 127-131 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohmura, K. et al.: "Immature multipotent hematopoietic progenitors lacking long-term bone marrow-reconstituting activity in the aortagonad-mesonephros region of murine day 10 fetuses"Journal of Immunology. 166. 3290-3296 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ikawa, T. et al: "Commitment to natural Killer clels requires the helix-loop-helix inhitibor Id2"Proc.Natl.Acad.Scl.USA. 98. 5164-5169 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsura, Y. et al.: "Stepwise lineage restriction of progenitors in lympho-myelopoiesis"International Review of Immunology. 20. 1-20 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Egawa, T. et al: "The earliest stages of B cell development require a chemokine stormal cell-derived factor/pre-B cell growth-stimulating factor"Immunity. 15. 1-20 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoi, M. et al.: "Two distinct steps of immigration hematopoietic progentitors into the early thymus anlage"Inlernational Immunology. 13. 1203-1211 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] katsura, Y.: "Redefinition of lymphoid progenitors"Nature Reviews Immunology. 2. 127-131 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohmura, K. et al.: "Immature multipotent hematopoietic progenitors lacking long-term bone marrow-reconstituting activity in the aorta-gonad-mesonephros region of murine day 10 fetuses."Journal of Immunology. 166. 3290-3296 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikawa, T. et al.: "Commitment to natural killer clels requires the helix-loop-helix inhitibor Id2"Proceedings of the National Academy of Sciences of the USA. 98. 5164-5169 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Katsura, Y. et al.: "Stepwise lineage restriction of progenitors in lympho-myelopoiesis"International Review of Immunology. 20. 1-20 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Egawa, T. et al.: "The earliest stages of B cell development require a chemokine stormal cell-derived factor/pre-B cell growth-stimulating fcator"Immunity. 15. 1-20 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Itoi, M. et al.: "Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage"International Immunology. 13. 1203-1211 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Katsura, Y.: "Redefiniation of lymphoid progenitors"Nature Reviews Immunology. 2. 127-131 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawamoto,H. et al.: "T cellprogenitors emerge earlier than B cell progenitors in the murine fetal liver."Immunity. 12. 441-450 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kina,T. et al.: "The monoclonal antibody TER-119 recognizes a molecule associated with glyco-phorin A and sepcifically marks the late stages of murine erythroid lineage."British Journal of Haematology. 109. 280-287 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shimizu,C. et al.: "Progression of T cell lineage restriciton in the earliest subpopulation of murine adult thymus visualized by the expression of lck proximal promoter activity."International Immunology. 13・1. 105-117 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohmura,K. et al.: "Immature multipotent hematopoietic progenitors lacking long-term bene marrow-reconstituting activity in the aorta-gonad-mesonephros region of murine day 10 fetuses."Journal of Immunology. 166. 3290-3296 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ikawa,T. et al.: "Commitment to natural killer clels requires the helix-loop-helix inhitibor Id2."Proceedings of the National Academy of Sciences of the USA. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Katsura,Y. et al.: "Stepwise lineage restriction of progenitors in lympho-myelopoiesis."International Review of Immunology. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] van Evijk,W. et al.: "Current Topics in Microbiology and Immunology"Springer, Germany. 210 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawamoto H.et al.: "Emergence of T cell lineage restricted progenitors at the earliest stage of hematopoiesis in the murine etal liver"Journal of Immunology. 162・5. 2725-2731 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] van Ewijk W.et al.: "Thymic miroenvironments, 3-D versus 2-D?"Seminars in Immunology. 11・1. 57-64 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawabata K.et al.: "A cell-autonomous requirement for CXCR4 in long-term lymphoid and myeloid reconstitution"Proc. Natl. Acad. Sci. USA. 96・10. 5663-5667 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohmura K.et al.: "Emmergence of T, B and myeloid lineage commitment as well as multipotent hematopoietic progenitors in the AGM region of day 10 fetuses of the mouse"Journal of Immunology. 163・9. 4788-4795 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikawa T.et al.: "Commitment of common T/NK progenitors to unipotent T and NK progenitors in the murine fetal thymus revealed by a single progenitor assay"Journal of Experimental Medicine. 190・11. 1617-1625 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawamoto H.et al.: "T cell progenitors emerge earlier than B cell progenitors in the murine fetal liver"Immunity. (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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