HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xu, Y. Articles by Kershaw, M. H. Search for Related Content PubMed PubMed Citation Articles by Xu, Y. Articles by Kershaw, M. H.

Differential Development of Murine Dendritic Cells by GM-CSF versus Flt3 Ligand Has Implications for Inflammation and Trafficking¹

Yuekang Xu^2,*,, Yifan Zhan, Andrew M. Lew, Shalin H. Naik^, and Michael H. Kershaw^2,*,

^* Cancer Immunology Research Program, Peter MacCallum Cancer Centre, Melbourne, Australia; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; The Netherlands Cancer Institute, Amsterdam, The Netherlands; and Department of Pathology, University of Melbourne, Australia

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^lowCD11b^high and CD24^highCD11b^low). Functionally, although comparable in T cell activation, GM/IL4-DCs produced more inflammatory mediators including TNF-, 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^highLy6C^highLy6G^– monocytes. Collectively, these data suggest that the GM/IL4-DCs are the equivalents of the TNF- 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Health and Medical Research Council of Australia (NH&MRC) and Juvenile Diabetes Research Foundation. Y.X. is supported by Peter Doherty Fellowship from NH&MRC 400426. S.H.N. was funded under NH&MRC (Program Grant number: 215203) but now is a Marie Curie Fellow funded by the European Union. Y.Z. is supported by RD Wright Fellowship from NH&MRC. A.M.L. is supported by Juvenile Diabetes Research Foundation and NH&MRC. M.H.K. is supported by fellowships from NH&MRC and National Breast Cancer Foundation of Australia.

² Address correspondence and reprint requests to Dr. Yuekang Xu or Dr. Michael H. Kershaw, Cancer Immunology Research Program, Peter MacCallum Cancer Centre, St. Andrews Place, Melbourne, Victoria, 3002 Australia. E-mail addresses: yuekang.xu{at}petermac.org or michael.kershaw{at}petermac.org

³ Abbreviations used in this paper: DC, dendritic cell; cDC, conventional DC; pre-DC, precursors of DC; pDC, plasmacytoid DC; Tip-DC, TNF- and inducible NO synthase-producing DCs; BM, bone marrow; Flt3L, fms-like tyrosine kinase 3 ligand; GM/IL4-DC, DC derived from GM-CSF/IL-4 culture; FL-DC, DC derived from Flt3L culture.

This article has been cited by other articles:

				M. A. Curran and J. P. Allison Tumor Vaccines Expressing Flt3 Ligand Synergize with CTLA-4 Blockade to Reject Preimplanted Tumors Cancer Res., October 1, 2009; 69(19): 7747 - 7755. [Abstract] [Full Text] [PDF]

				D. Kingston, M. A. Schmid, N. Onai, A. Obata-Onai, D. Baumjohann, and M. G. Manz The concerted action of GM-CSF and Flt3-ligand on in vivo dendritic cell homeostasis Blood, July 23, 2009; 114(4): 835 - 843. [Abstract] [Full Text] [PDF]

				K. L. Wong, L. F. M. Tang, F. C. Lew, H. S. K. Wong, Y. L. Chua, P. A. MacAry, and D. M. Kemeny CD44high Memory CD8 T Cells Synergize with CpG DNA to Activate Dendritic Cell IL-12p70 Production J. Immunol., July 1, 2009; 183(1): 41 - 50. [Abstract] [Full Text] [PDF]

				H. S. Goodridge, T. Shimada, A. J. Wolf, Y.-M. S. Hsu, C. A. Becker, X. Lin, and D. M. Underhill Differential Use of CARD9 by Dectin-1 in Macrophages and Dendritic Cells J. Immunol., January 15, 2009; 182(2): 1146 - 1154. [Abstract] [Full Text] [PDF]

				K.-C. Sheng, M. Kalkanidis, D. S. Pouniotis, M. D. Wright, G. A. Pietersz, and V. Apostolopoulos The Adjuvanticity of a Mannosylated Antigen Reveals TLR4 Functionality Essential for Subset Specialization and Functional Maturation of Mouse Dendritic Cells J. Immunol., August 15, 2008; 181(4): 2455 - 2464. [Abstract] [Full Text] [PDF]

				V. Carregaro, J. G. Valenzuela, T. M. Cunha, W. A. Verri Jr., R. Grespan, G. Matsumura, J. M. C. Ribeiro, D.-E. Elnaiem, J. S. Silva, and F. Q. Cunha Phlebotomine salivas inhibit immune inflammation-induced neutrophil migration via an autocrine DC-derived PGE2/IL-10 sequential pathway J. Leukoc. Biol., July 1, 2008; 84(1): 104 - 114. [Abstract] [Full Text] [PDF]