Abstract
Here, we report that the number of CD11c(+)CD3(-) B220(-) cells increases in autoimmune-prone male (NZW x BXSB)F1 (W/BF1) mice with age. The CD11c(+)CD3(-)B220(-) cells from W/BF1 mice show a typical stellate shape and induce the proliferation of T cells. In the CD11c(+)CD3(-)B220(-) cells from W/BF1 mice, CD11b (Mac-1alpha), NK 1.1, and CD95 (Fas) are upregulated in comparison with normal mice, while the expression of CD8alpha, CD117 (c-kit), CD135 (Flk-2/Flt-3), and Sca-1 decreases. There is a significant increase in Flt-3L (FL) mRNA in the bone marrow of W/BF1 mice with age. Moreover, activated hemopoietic cells express high levels of FL. The injection of CD11c(+)CD3(-)B220(-) cells from old W/BF1 mice to young W/BF1 mice transiently induces autoimmune disease (thrombocytopenia). These results suggest that hyperproduction of FL from activated hemopoietic cells induces a dramatic increase in the number of dendritic cells in aged W/BF1 mice, followed by the acceleration of autoimmunity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Marrow / metabolism
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CD11 Antigens / biosynthesis
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CD4-Positive T-Lymphocytes / metabolism
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CD8 Antigens / biosynthesis
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Cell Division
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Cell Line
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Cell Membrane / metabolism
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Crosses, Genetic
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Dendritic Cells / cytology*
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Dendritic Cells / metabolism
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Endocytosis
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Flow Cytometry
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Integrin alphaXbeta2 / biosynthesis
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Leukocytes, Mononuclear / metabolism
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Lymphocytes / metabolism
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Membrane Proteins / biosynthesis
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Mice
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Phagocytosis
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins c-kit / biosynthesis
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RNA, Messenger / metabolism
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Receptor Protein-Tyrosine Kinases / biosynthesis
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Reverse Transcriptase Polymerase Chain Reaction
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Thrombocytopenia / metabolism
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Time Factors
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Up-Regulation
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fas Receptor / biosynthesis
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fms-Like Tyrosine Kinase 3
Substances
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CD11 Antigens
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CD8 Antigens
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CD8alpha antigen
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Integrin alphaXbeta2
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Membrane Proteins
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Proto-Oncogene Proteins
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RNA, Messenger
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fas Receptor
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flt3 ligand protein
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Flt3 protein, mouse
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Proto-Oncogene Proteins c-kit
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Receptor Protein-Tyrosine Kinases
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fms-Like Tyrosine Kinase 3