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Brief Definitive Report

¹ DNAX Research Institute, Palo Alto, CA 94304
² Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France

Address correspondence to Yong-Jun Liu, DNAX Research Institute, 901 California Ave., Palo Alto, CA 94304-1104. Phone: 650-496-1157; Fax: 650-496-1200; E-mail: yong-jun.liu{at}dnax.org

Plasmacytoid predendritic cells or type 1 interferon (IFN)-producing cells (IPCs) have recently been identified in mice. Although culture systems giving rise to different murine dendritic cell subsets have been established, the developmental regulation of murine plasmacytoid IPCs and the culture conditions leading to their generation remain unknown. Here we show that large numbers of over 40% pure CD11c⁺CD11b^-B220⁺Gr-1⁺ IPCs can be generated from mouse bone marrow cultures with FLT3-ligand. By contrast GM-CSF or TNF-, which promote the generation of CD11c⁺CD11b⁺B220^- myeloid DCs, block completely the development of IPCs. IPCs generated display similar features to human IPCs, such as the plasmacytoid morphology, the ability to produce large amounts of IFN- in responses to herpes simplex virus, and the capacity to respond to ligands for Toll-like receptor 9 (TLR-9; CpG ODN 1668), but not to ligands for TLR-4 (lipopolysaccharide [LPS]). Unlike human IPCs which produce little IL-12p70, mouse IPCs produce IL-12p70 in response to CpG ODN 1668 and herpes simplex virus. This study demonstrates that the development of murine CD11c⁺CD11b^-B220⁺Gr-1⁺ IPCs and CD11c⁺CD11b⁺B220^- myeloid DCs is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. Human IPCs and mouse IPCs display different ability to produce IL-12p70. Large numbers of mouse IPCs can now be obtained from total bone marrow culture.

Key Words: pre-DC2 • IPC • T lymphocyte • antiviral immune response • innate immunity

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• Chen, W., Antonenko, S., Sederstrom, J. M., Liang, X., Chan, A. S. H., Kanzler, H., Blom, B., Blazar, B. R., Liu, Y.-J. (2004). Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors. Blood 103: 2547-2553 [Abstract] [Full Text]  
• Schiavoni, G., Mattei, F., Borghi, P., Sestili, P., Venditti, M., Morse, H. C. III, Belardelli, F., Gabriele, L. (2004). ICSBP is critically involved in the normal development and trafficking of Langerhans cells and dermal dendritic cells. Blood 103: 2221-2228 [Abstract] [Full Text]  
• Diebold, S. S., Kaisho, T., Hemmi, H., Akira, S., Reis e Sousa, C. (2004). Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA. Science 303: 1529-1531 [Abstract] [Full Text]  
• Salio, M., Palmowski, M. J., Atzberger, A., Hermans, I. F., Cerundolo, V. (2004). CpG-matured Murine Plasmacytoid Dendritic Cells Are Capable of In Vivo Priming of Functional CD8 T Cell Responses to Endogenous but Not Exogenous Antigens. JEM 199: 567-579 [Abstract] [Full Text]  
• Zhang, Y., Yoneyama, H., Wang, Y., Ishikawa, S., Hashimoto, S.-i., Gao, J.-L., Murphy, P., Matsushima, K. (2004). Mobilization of Dendritic Cell Precursors Into the Circulation by Administration of MIP-1{alpha} in Mice. JNCI J Natl Cancer Inst 96: 201-209 [Abstract] [Full Text]  
• Li, Q., Pan, P.-Y., Gu, P., Xu, D., Chen, S.-H. (2004). Role of Immature Myeloid Gr-1+ Cells in the Development of Antitumor Immunity. Cancer Res. 64: 1130-1139 [Abstract] [Full Text]  
• Asselin-Paturel, C., Brizard, G., Pin, J.-J., Briere, F., Trinchieri, G. (2003). Mouse Strain Differences in Plasmacytoid Dendritic Cell Frequency and Function Revealed by a Novel Monoclonal Antibody. J. Immunol. 171: 6466-6477 [Abstract] [Full Text]  
• Spies, B., Hochrein, H., Vabulas, M., Huster, K., Busch, D. H., Schmitz, F., Heit, A., Wagner, H. (2003). Vaccination with Plasmid DNA Activates Dendritic Cells via Toll-Like Receptor 9 (TLR9) but Functions in TLR9-Deficient Mice. J. Immunol. 171: 5908-5912 [Abstract] [Full Text]  
• Marshall, J. D., Hessel, E. M., Gregorio, J., Abbate, C., Yee, P., Chu, M., Nest, G. V., Coffman, R. L., Fearon, K. L. (2003). Novel chimeric immunomodulatory compounds containing short CpG oligodeoxyribonucleotides have differential activities in human cells. Nucleic Acids Res 31: 5122-5133 [Abstract] [Full Text]  
• Mellor, A. L., Baban, B., Chandler, P., Marshall, B., Jhaver, K., Hansen, A., Koni, P. A., Iwashima, M., Munn, D. H. (2003). Cutting Edge: Induced Indoleamine 2,3 Dioxygenase Expression in Dendritic Cell Subsets Suppresses T Cell Clonal Expansion. J. Immunol. 171: 1652-1655 [Abstract] [Full Text]  
• Lund, J., Sato, A., Akira, S., Medzhitov, R., Iwasaki, A. (2003). Toll-like Receptor 9-mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells. JEM 198: 513-520 [Abstract] [Full Text]  
• D'Amico, A., Wu, L. (2003). The Early Progenitors of Mouse Dendritic Cells and Plasmacytoid Predendritic Cells Are within the Bone Marrow Hemopoietic Precursors Expressing Flt3. JEM 198: 293-303 [Abstract] [Full Text]  

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