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J Immunol ; 167(1): 242-9, 2001 Jul 01.
Article in English | MEDLINE | ID: mdl-11418655

ABSTRACT

The human B-myb gene encodes a transcriptional regulator that plays an important role in cell cycle progression, differentiation, and survival. To assess the in vivo role of B-myb, we investigated the phenotype of mouse transgenic lines in which B-Myb expression in lymphoid tissues was driven by the LCK proximal promoter. Overexpression of B-Myb had no measurable effect on the subsets of splenic and thymic lymphocytes, but was associated with increased expression of Fas ligand in NK and T cells. B-Myb-overexpressing splenocytes expressed higher IFN-gamma levels and contained higher percentages of cytokine-producing cells than wild-type (wt) splenocytes, as detected by Western blot analysis and ELISPOT assays, respectively. Ex vivo-cultured transgenic thymocytes and splenocytes had decreased survival compared with the corresponding cells from wt mice, possibly dependent on increased expression of Fas ligand. In addition, Fas ligand-dependent cytotoxicity of transgenic T and NK cells was significantly higher than that mediated by their wt counterparts. Together, these results indicate that B-Myb overexpression results in T and NK cell activation and increased cytotoxicity. Therefore, in addition to its well-established role in proliferation and differentiation, B-myb also appears to be involved in activation of NK and T cells and in their regulation of Fas/Fas ligand-mediated cytotoxicity


Subject(s)
Cell Cycle Proteins , Cytotoxicity, Immunologic , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Killer Cells, Natural/immunology , Lymphocyte Activation , Membrane Glycoproteins/physiology , T-Lymphocytes, Cytotoxic/immunology , Trans-Activators/biosynthesis , Trans-Activators/genetics , fas Receptor/physiology , Animals , Cell Survival/genetics , Cell Survival/immunology , Cells, Cultured , Crosses, Genetic , Cytotoxicity Tests, Immunologic , Cytotoxicity, Immunologic/genetics , Fas Ligand Protein , Humans , Interferon-gamma/biosynthesis , Interferon-gamma/genetics , Jurkat Cells , Killer Cells, Natural/cytology , Ligands , Lymphocyte Activation/genetics , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics , Membrane Glycoproteins/biosynthesis , Membrane Glycoproteins/genetics , Mice , Mice, Inbred C57BL , Mice, Transgenic , T-Lymphocytes, Cytotoxic/cytology
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