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The Role of CD45 in Leukocyte Differentiation and Function

Research Project

Project/Area Number 06044178
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionKYUSHU UNEVERSITY

Principal Investigator

KISHIHARA Kenji  Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Research Associate, 生体防御医学研究所, 助手 (80214774)

Co-Investigator(Kenkyū-buntansha) MAK Tak w  Division of Molecular and Cellular Immunology, Ontario Cancer Institute, 細胞及び分子生物学部門, 部門長
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1995: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
KeywordsCD45 / Tyrosine Phosphatase / T cell / B cell / NK cell / Gene Targeting / 白血球 / 免疫異常
Research Abstract

We have analyzed the involvement of CD45 in development, activation and function of T,B and NK cells using CD45 exon 6-deficient mice (CD45-/-mice) in this research project.
In the analysis of CD45-deicient T cell receptor (TCR)-transgenic CD45 mice, it was suggested that CD45 is involved in the signal transduction for positive selection of T cells and allelic exclusion of TCRalpha chain. CD45-defective thymocytes and peripheral mature T cells from CD45-/- mice showed virtually no response to TCR-crosslinking suggesting that CD45 is crucial for a TCR-mediated signaling mechanism. Furthermore, Antigen-specific response including cytolytic T lymphocyte and helper T cell function could not observed in CD45^- T cells from CD45-/- mice. Moreover, it was demonstrated that CD45 is involved in the signal transduction during maturation of Vgamma3 T cells in epidermis and fetal thymus.
B cell development in the CD45-/- mice was enhanced throughout their lives (the approximately twice more increased number of B cells (sIgM^+) in the spleen). CD45-defective B cells from CD45-/-mice showed intact B cell functions including T -dependent and -independent antigen-specific antibody production and class switching in vivo if normal CD4^+ T cells were adoptively transferred into the knock out mice.
The NK activity of the splenocytes from CD45-/- mice was markedly elevated because of the increased number of NK cells in the CD45-/- mice. Cytolytic and ADCC activities were intact in the NK and LAK cells despite no CD45 surface expression.
From the above data, it's clear that requirement of CD45 for development and function is different in T,B and NK cells.

Report

(2 results)
  • 1995 Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Kong Y.-Y.,K.Kishihara,H.Yoshida,et al.: "Generation of T cells with differential responses to alloantigens in CD45 exon 6-deficient mice" The Journal of Immunology. 154. 5725-5735 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kong Y.-Y.,K.Kishihara,H.Sumichika,et al.: "Differential requirements of CD45 for lymphocyte development and function" European Journal of Immunology. 25. 3431-3436 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kawai K.,K.Kishihara,et al.: "Impaired development of Vγ3 dendritoc epidermal T cells in p56^<lck> protein tyrosinekinase-deficient and CD45 protein tyrosine phosphatase-deficient mice" Journal of Experimental Medicine. 181. 345-349 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kong, Y.-Y., K.Kishihara, H.Yoshida et al.: "Generation of T cells with differential responses to alloantigens in CD45 exon 6-deficient mice" The Journal of Immunology. 154. 5725-5735 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kong Y.-Y., K.Kishihara, H.Sumichika et al.: "Differential requirements of CD45 for lymphocyte development and function" European Journal of Immunology. 25. 3431-3436 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kawai, K., K.Kishihara et al.: "Impaired development of Vgamma3 dendritoc epidermal T cells in p56^<ICK> protein tyrosine kinase-deficient and CD45 protein tyrosine phosphatase-deficient mice" Journal of Experimental Medicine. 181. 345-349 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kazuo Kawai: "Impaired Development of Vγ3 Dendritic Epidermal T Cells in p56^<lck> Protein Tyrosine Kinase-deficient and CD45 Protein Tyrosine Phosphatase-deficient Mice" Journal of Experimental Medicine. 181. 345-349 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Josef M.Penninger: "The Protein Phosphatase CD45 Controls Positive Thymocyte Selection and Allelic Exclusion of TCRα Chians" (投稿中).

    • Related Report
      1994 Annual Research Report
  • [Publications] Josef M.Penninger: (投稿中).

    • Related Report
      1994 Annual Research Report
  • [Publications] Valerie A.Wallace: "Alterations in the Level of CD45 Surface Expression Affect the Outcome of Thymic Selection" (投稿中).

    • Related Report
      1994 Annual Research Report
  • [Publications] Young-Yun Kong: "Generation of T Cells with Differential Responses in CD45 Exon 6-deficient Mice" (投稿中).

    • Related Report
      1994 Annual Research Report
  • [Publications] Young-Yun Kong: "Retention of Antigen-specific Responses in CD45 Exon 6-deficient Mice" (投稿中).

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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