Differential development of murine dendritic cells by GM-CSF versus flt3 ligand has implications for inflammation and trafficking
- Author(s)
- Xu, YK; Zhan, YF; Lew, AM; Naik, SH; Kershaw, MH;
- Details
- Publication Year 2007-12-01,Volume 179,Issue #11,Page 7577-7584
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- 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 iinmunotherapy, 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-a 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.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- COLONY-STIMULATING FACTOR; BONE-MARROW CULTURES; MONOCYTE CHEMOATTRACTANT PROTEIN-1; NITRIC-OXIDE SYNTHASE; BACTERIAL-INFECTION; STEADY-STATE; T-CELLS; MOUSE; PRECURSORS; GENERATION
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Creation Date: 2007-12-01 12:00:00