Marked Increase in Number of Dendritic Cells in Autoimmune‐Prone (NZW × BXSB)F1 Mice with Age

Here, we report that the number of CD11c+CD3− B220− cells increases in autoimmune‐prone male (NZW × 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‐1α), NK 1.1, and CD95 (Fas) are upregulated in comparison with normal mice, while the expression of CD8α, 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.

[1]  O. Pfister,et al.  Cell-surface trafficking and release of flt3 ligand from T lymphocytes is induced by common cytokine receptor gamma-chain signaling and inhibited by cyclosporin A. , 2001, Blood.

[2]  S. Ikehara,et al.  Age‐Dependent Abnormalities of Hematopoietic Stem Cells in (NZW × BXSB)F1 Mice , 1999, Stem cells.

[3]  W. Fanslow,et al.  Synergistic action of fms-like tyrosine kinase 3 ligand and CD40 ligand in the induction of dendritic cells and generation of antitumor immunity in vivo. , 1999, Journal of immunology.

[4]  K. Shortman,et al.  Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. , 1997, Journal of immunology.

[5]  S. Ikehara,et al.  The appearance of unusual phenotypic cells (CD4+ Mac-1+ class II+) in the liver of (NZW x BXSB)F1 mice is possibly an animal model for autoimmune hepatitis. , 1997, Immunobiology.

[6]  Robert E. Miller,et al.  Flt3 ligand induces tumor regression and antitumor immune responses in vivo , 1997, Nature Medicine.

[7]  Francesca Granucci,et al.  Maturation Stages of Mouse Dendritic Cells in Growth Factor–dependent Long-Term Cultures , 1997, The Journal of experimental medicine.

[8]  K. Sullivan,et al.  Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity. , 1996, The New England journal of medicine.

[9]  T. Mcclanahan,et al.  Biochemical and genetic characterization of multiple splice variants of the Flt3 ligand. , 1996, Blood.

[10]  E. Maraskovsky,et al.  Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified , 1996, The Journal of experimental medicine.

[11]  K. Shortman,et al.  Effects of excess GM-CSF levels on hematopoiesis and leukemia development in GM-CSF/max 41 double transgenic mice. , 1996, Leukemia.

[12]  J. Banchereau,et al.  Interleukin-3 cooperates with tumor necrosis factor alpha for the development of human dendritic/Langerhans cells from cord blood CD34+ hematopoietic progenitor cells. , 1996, Blood.

[13]  Warren Strober,et al.  Dominant interfering fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome , 1995, Cell.

[14]  R. Steinman,et al.  The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing , 1995, Nature.

[15]  Y. Adachi,et al.  Effect of bone marrow transplantation on antiphospholipid antibody syndrome in murine lupus mice. , 1995, Immunobiology.

[16]  R. Engelman,et al.  Development and characterization of monoclonal antiplatelet autoantibodies from autoimmune thrombocytopenic purpura-prone (NZW x BXSB)F1 mice. , 1993, Blood.

[17]  R. Steinman,et al.  Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor , 1992, The Journal of experimental medicine.

[18]  N. Copeland,et al.  Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis , 1992, Nature.

[19]  R. Steinman,et al.  Dendritic cells pulsed with protein antigens in vitro can prime antigen- specific, MHC-restricted T cells in situ [published erratum appears in J Exp Med 1990 Oct 1;172(4):1275] , 1990, The Journal of experimental medicine.

[20]  R. Steinman,et al.  The distinct leukocyte integrins of mouse spleen dendritic cells as identified with new hamster monoclonal antibodies , 1990, The Journal of experimental medicine.

[21]  Y. Tomiyama,et al.  Analyses of thrombocytopenia in idiopathic thrombocytopenic purpura-prone mice by platelet transfer experiments between (NZW x BXSB)F1 and normal mice. , 1990, Blood.

[22]  S. Nomura,et al.  (NZW x BXSB)F1 mouse. A new animal model of idiopathic thrombocytopenic purpura , 1988, The Journal of experimental medicine.

[23]  R. Balderas,et al.  The effect of thymectomy on lupus-prone mice. , 1984, Journal of immunology.

[24]  F. Dixon,et al.  The role of hypertension in the vascular disease and myocardial infarcts associated with murine systemic lupus erythematosus. , 1983, Arthritis and rheumatism.

[25]  S. Izui,et al.  (NZW x BXSB)F1 hybrid. A model of acute lupus and coronary vascular disease with myocardial infarction , 1981, The Journal of experimental medicine.

[26]  R. Steinman,et al.  Identification of a novel cell type in peripheral lymphoid organs of mice. IV. Identification and distribution in mouse spleen , 1975, The Journal of experimental medicine.

[27]  R. Steinman,et al.  IDENTIFICATION OF A NOVEL CELL TYPE IN PERIPHERAL LYMPHOID ORGANS OF MICE , 1973, The Journal of experimental medicine.

[28]  S. Ikehara,et al.  Expression of CD45-restricted form B in (NZW x BXSB) F1 and MRL/Mp-lpr/lpr mice. , 1996, Autoimmunity.

[29]  S. Ikehara,et al.  Functional analyses of B cells in (NZW x BXSB) F1 mice. , 1993, Autoimmunity.

[30]  足立靖 Analyses of thymic abnormalities in autoimmune-prone(NZW x BXSB)F1 mice , 1993 .

[31]  R. Steinman,et al.  The dendritic cell system and its role in immunogenicity. , 1991, Annual review of immunology.