1995 Fiscal Year Final Research Report Summary
The Role of CD45 in Leukocyte Differentiation and Function
| Project/Area Number |
06044178
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | KYUSHU UNEVERSITY |
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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)
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| 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
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| Project Period (FY) |
1994 – 1995
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| Keywords | CD45 / Tyrosine Phosphatase / T cell / B cell / NK cell / Gene Targeting |
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| 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.
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