Marked increase in number of dendritic cells in autoimmune-prone (NZW x BXSB)F1 mice with age

Stem Cells. 2002;20(1):61-72. doi: 10.1634/stemcells.20-1-61.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow / metabolism
  • CD11 Antigens / biosynthesis
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8 Antigens / biosynthesis
  • Cell Division
  • Cell Line
  • Cell Membrane / metabolism
  • Crosses, Genetic
  • Dendritic Cells / cytology*
  • Dendritic Cells / metabolism
  • Endocytosis
  • Flow Cytometry
  • Integrin alphaXbeta2 / biosynthesis
  • Leukocytes, Mononuclear / metabolism
  • Lymphocytes / metabolism
  • Membrane Proteins / biosynthesis
  • Mice
  • Phagocytosis
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-kit / biosynthesis
  • RNA, Messenger / metabolism
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thrombocytopenia / metabolism
  • Time Factors
  • Up-Regulation
  • fas Receptor / biosynthesis
  • fms-Like Tyrosine Kinase 3

Substances

  • CD11 Antigens
  • CD8 Antigens
  • CD8alpha antigen
  • Integrin alphaXbeta2
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • fas Receptor
  • flt3 ligand protein
  • Flt3 protein, mouse
  • Proto-Oncogene Proteins c-kit
  • Receptor Protein-Tyrosine Kinases
  • fms-Like Tyrosine Kinase 3