J. Exp. Med., Volume 189, Number 12, June 21, 1999 1981-1986

Interleukin 12-dependent Interferon  Production by CD8⁺ Lymphoid Dendritic Cells

By Toshiaki Ohteki,^* Taro Fukao,^* Kazutomo Suzue,^* Chikako Maki,^* Mamoru Ito, Masataka Nakamura,^§ and Shigeo Koyasu^*

From the ^* Department of Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan; the  Laboratory of Immunology, Central Institute for Experimental Animals, Kawasaki 216-0001, Japan; and the ^§ Human Gene Sciences Center, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113, Japan

We investigated the role of antigen-presenting cells in early interferon (IFN)- production in normal and recombinase activating gene 2-deficient (Rag-2^/) mice in response to Listeria monocytogenes (LM) infection and interleukin (IL)-12 administration. Levels of serum IFN- in Rag-2^/ mice were comparable to those of normal mice upon either LM infection or IL-12 injection. Depletion of natural killer (NK) cells by administration of anti-asialoGM1 antibodies had little effect on IFN- levels in the sera of Rag-2^/ mice after LM infection or IL-12 injection. Incubation of splenocytes from NK cell-depleted Rag-2^/ mice with LM resulted in the production of IFN- that was completely blocked by addition of anti-IL-12 antibodies. Both dendritic cells (DCs) and monocytes purified from splenocytes were capable of producing IFN- when cultured in the presence of IL-12. Intracellular immunofluorescence analysis confirmed the IFN- production from DCs. It was further shown that IFN- was produced predominantly by CD8⁺ lymphoid DCs rather than CD8 myeloid DCs. Collectively, our data indicated that DCs are potent in producing IFN- in response to IL-12 produced by bacterial infection and play an important role in innate immunity and subsequent T helper cell type 1 development in vivo.

recombinase-activating gene 2 knockout mouse;  nonobese diabetic-severe combined immunodeficiency disease mouse;  _c knockout mouse;  natural killer cells;  Listeria monocytogenes

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• Kirby, A. C., Yrlid, U., Svensson, M., Wick, M. J. (2001). Differential Involvement of Dendritic Cell Subsets During Acute Salmonella Infection. J. Immunol. 166: 6802-6811 [Abstract] [Full Text]  
• Manz, M. G., Traver, D., Miyamoto, T., Weissman, I. L., Akashi, K. (2001). Dendritic cell potentials of early lymphoid and myeloid progenitors. Blood 97: 3333-3341 [Abstract] [Full Text]  
• Kang, H., Suzuki, Y. (2001). Requirement of Non-T Cells That Produce Gamma Interferon for Prevention of Reactivation of Toxoplasma gondii Infection in the Brain. Infect. Immun. 69: 2920-2927 [Abstract] [Full Text]  
• Hochrein, H., Shortman, K., Vremec, D., Scott, B., Hertzog, P., O'Keeffe, M. (2001). Differential Production of IL-12, IFN-{{alpha}}, and IFN-{{gamma}} by Mouse Dendritic Cell Subsets. J. Immunol. 166: 5448-5455 [Abstract] [Full Text]  
• Horwood, N. J., Elliott, J., Martin, T. J., Gillespie, M. T. (2001). IL-12 Alone and in Synergy with IL-18 Inhibits Osteoclast Formation In Vitro. J. Immunol. 166: 4915-4921 [Abstract] [Full Text]  
• Fukao, T., Frucht, D. M., Yap, G., Gadina, M., O'Shea, J. J., Koyasu, S. (2001). Inducible Expression of Stat4 in Dendritic Cells and Macrophages and Its Critical Role in Innate and Adaptive Immune Responses. J. Immunol. 166: 4446-4455 [Abstract] [Full Text]  
• Ito, T., Amakawa, R., Inaba, M., Ikehara, S., Inaba, K., Fukuhara, S. (2001). Differential Regulation of Human Blood Dendritic Cell Subsets by IFNs. J. Immunol. 166: 2961-2969 [Abstract] [Full Text]  
• Schindler, H., Lutz, M. B., Rollinghoff, M., Bogdan, C. (2001). The Production of IFN-{{gamma}} by IL-12/IL-18-Activated Macrophages Requires STAT4 Signaling and Is Inhibited by IL-4. J. Immunol. 166: 3075-3082 [Abstract] [Full Text]  
• Seki, E., Tsutsui, H., Nakano, H., Tsuji, N. M., Hoshino, K., Adachi, O., Adachi, K., Futatsugi, S., Kuida, K., Takeuchi, O., Okamura, H., Fujimoto, J., Akira, S., Nakanishi, K. (2001). Lipopolysaccharide-Induced IL-18 Secretion from Murine Kupffer Cells Independently of Myeloid Differentiation Factor 88 That Is Critically Involved in Induction of Production of IL-12 and IL-1{{beta}}. J. Immunol. 166: 2651-2657 [Abstract] [Full Text]  
• Hope, J. C., Sopp, P., Collins, R. A, Howard, C. J. (2001). Differences in the induction of CD8+ T cell responses by subpopulations of dendritic cells from afferent lymph are related to IL-1{alpha} secretion. J. Leukoc. Biol. 69: 271-279 [Abstract] [Full Text]  
• Bregenholt, S., Berche, P., Brombacher, F., Di Santo, J. P. (2001). Conventional {{alpha}}{{beta}} T Cells Are Sufficient for Innate and Adaptive Immunity Against Enteric Listeria monocytogenes. J. Immunol. 166: 1871-1876 [Abstract] [Full Text]  
• Sung, S.-s. J., Rose, C. E. Jr., Fu, S. M. (2001). Intratracheal Priming with Ovalbumin- and Ovalbumin 323-339 Peptide-Pulsed Dendritic Cells Induces Airway Hyperresponsiveness, Lung Eosinophilia, Goblet Cell Hyperplasia, and Inflammation. J. Immunol. 166: 1261-1271 [Abstract] [Full Text]  
• Drake, D. R. III, Shawver, M. L., Hadley, A., Butz, E., Maliszewski, C., Lukacher, A. E. (2001). Induction of Polyomavirus-Specific CD8+ T Lymphocytes by Distinct Dendritic Cell Subpopulations. J. Virol. 75: 544-547 [Abstract] [Full Text]  
• Grohmann, U., Fallarino, F., Silla, S., Bianchi, R., Belladonna, M. L., Vacca, C., Micheletti, A., Fioretti, M. C., Puccetti, P. (2001). CD40 Ligation Ablates the Tolerogenic Potential of Lymphoid Dendritic Cells. J. Immunol. 166: 277-283 [Abstract] [Full Text]  
• Blom, B., Ho, S., Antonenko, S., Liu, Y.-J. (2000). Generation of Interferon {{alpha}}-producing Predendritic Cell (Pre-DC)2 from Human CD34+ Hematopoietic Stem Cells. J. Exp. Med. 192: 1785-1796 [Abstract] [Full Text]  
• Hussell, T., Openshaw, P. J. M. (2000). IL-12-Activated NK Cells Reduce Lung Eosinophilia to the Attachment Protein of Respiratory Syncytial Virus But Do Not Enhance the Severity of Illness in CD8 T Cell-Immunodeficient Conditions. J. Immunol. 165: 7109-7115 [Abstract] [Full Text]  

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