title: Differential development of murine dendritic cells by GM-CSF versus Flt3 ligand has implications for inflammation and trafficking.
abstract: To gain ample numbers of dendritic cells (DCs) for investigation, or for immunotherapy, the culture of DC precursors from bone marrow in either GM-CSF and IL-4 (GM/IL4-DCs) or Flt3L (FL-DCs) has often been used. Despite their common use, the relationship of these culture-derived DCs to those in vivo, and their relative potential for use in immunotherapy, needs further elucidation. In this study we found that in contrast to FL-DCs, highly purified GM/IL4-DCs were larger and more granular, surface Mac-3(+), and were comprised of two populations (CD24(low)CD11b(high) and CD24(high)CD11b(low)). Functionally, although comparable in T cell activation, GM/IL4-DCs produced more inflammatory mediators including TNF-alpha, IL-10, CCL-2, and NO than FL-DCs upon TLR ligation. However, FL-DCs migrated more efficiently to draining lymph nodes after s.c. injection and produced a different profile of cytokines to GM/IL4-DCs. Developmentally, unlike GM/IL4-DCs, FL-DCs cannot be differentiated from CD11b(high)Ly6C(high)Ly6G(-) monocytes. Collectively, these data suggest that the GM/IL4-DCs are the equivalents of the TNF-alpha and inducible NO synthase producing DCs in vivo that emerge after inflammation whereas FL-DCs better represent the steady-state resident DCs. The differences between GM/IL4-DCs and FL-DCs have serious implications for DC-based immunotherapeutic strategies.
authors.affiliation: Cancer Immunology Research Program, Peter MacCallum Cancer Centre, Melbourne, Australia. yuekang.xu@petermac.org
authors.forename: Yuekang
authors.initials: Y
authors.lastname: Xu
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhan
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lew
authors.forename: Shalin H
authors.initials: SH
authors.lastname: Naik
authors.forename: Michael H
authors.initials: MH
authors.lastname: Kershaw
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology; D007279:Injections, Subcutaneous; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D016207:Cytokines; D008024:Ligands; D008565:Membrane Proteins; D051193:Toll-Like Receptors; C084881:flt3 ligand protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor