title: Comparison of the functional properties of murine dendritic cells generated in vivo with Flt3 ligand, GM-CSF and Flt3 ligand plus GM-SCF.
abstract: Flt3 ligand (FL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are important growth factors for dendritic cells (DC). Substantial numbers of DC can be generated in vivo following the administration of either factor. We sought to extend our knowledge of the functional properties of these cells including their ability to prime naïve CD8(+) T cells. In addition, we compared the nature of the DC generated in vivo with the single cytokines to those generated with the combination of FL+polyethylene glycol-modified GM-CSF (pGM-CSF). Treatment with FL+pGM-CSF yielded greater numbers of both CD11b(low) and CD11b(high) DC than with either cytokine alone, and these DC were more efficient at antigen (Ag) capture. The FL+pGM-CSF-generated CD11b(low) DC lacked expression of CD8alpha. Following treatment with LPS in vivo, all DC subsets upregulated CD40, CD80, CD86, and MHC class II expression, but surprisingly Ag capture was not downregulated and some DC subsets retained expression of intracellular MHC class II vesicles. Thus, even after activation in vivo with LPS, DC retained Ag capture properties of immature DC, and Ag presentation/costimulation properties of mature DC. Though all DC subsets stimulated CD4(+) T cell proliferation equivalently, FL-generated DC were more efficient at priming Ag-specific CD8(+) cytolytic T cells than DC generated with either pGM-CSF alone or FL+pGM-CSF, and CD11b(high) DC were more efficient at priming CD8(+) T cells than CD11b(low) DC.
authors.affiliation: Department of Immunobiology, Immunex Corporation, Seattle, Washington 98101, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Daro
authors.forename: Eric
authors.initials: E
authors.lastname: Butz
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Smith
authors.forename: Mark
authors.initials: M
authors.lastname: Teepe
authors.forename: Charles R
authors.initials: CR
authors.lastname: Maliszewski
authors.forename: Hilary J
authors.initials: HJ
authors.lastname: McKenna
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D039481:CD11b Antigen / Q000276:immunology*; D015704:CD4 Antigens; D019013:CD40 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002455:Cell Division; D022162:Cytoplasmic Vesicles; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D007424:Intracellular Fluid; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D039481:CD11b Antigen; D015704:CD4 Antigens; D019013:CD40 Antigens; D016827:CD8 Antigens; C497964:CD86 protein, human; C431698:CD8alpha antigen; C497965:Cd86 protein, mouse; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C084881:flt3 ligand protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor