Original Article

B7-DC, a New Dendritic Cell Molecule with Potent Costimulatory Properties for T Cells

Correspondence to: Drew M. Pardoll, Department of Oncology, Johns Hopkins School of Medicine, 1650 Orleans St.-1, CRB-Rm. 440, Baltimore, MD 21231. Tel:410-955-7866 Fax:410-614-0549 E-mail:dmpardol{at}jhmi.edu.

Dendritic cells (DCs), unique antigen-presenting cells (APCs) with potent T cell stimulatory capacity, direct the activation and differentiation of T cells by providing costimulatory signals. As such, they are critical regulators of both natural and vaccine-induced immune responses. A new B7 family member, B7-DC, whose expression is highly restricted to DCs, was identified among a library of genes differentially expressed between DCs and activated macrophages. B7-DC fails to bind the B7.1/2 receptors CD28 and cytotoxic T lymphocyte–associated antigen (CTLA)-4, but does bind PD-1, a receptor for B7-H1/PD-L1. B7-DC costimulates T cell proliferation more efficiently than B7.1 and induces a distinct pattern of lymphokine secretion. In particular, B7-DC strongly costimulates interferon but not interleukin (IL)-4 or IL-10 production from isolated naive T cells. These properties of B7-DC may account for some of the unique activity of DCs, such as their ability to initiate potent T helper cell type 1 responses.

Key Words: dendritic cells, T cell activation, B7, interferon , costimulatory molecule

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• Radhakrishnan, S., Nguyen, L. T., Ciric, B., Ure, D. R., Zhou, B., Tamada, K., Dong, H., Tseng, S.-Y., Shin, T., Pardoll, D. M., Chen, L., Kyle, R. A., Rodriguez, M., Pease, L. R. (2003). Naturally Occurring Human IgM Antibody That Binds B7-DC and Potentiates T Cell Stimulation by Dendritic Cells. J. Immunol. 170: 1830-1838 [Abstract] [Full Text]  
• Brown, J. A., Dorfman, D. M., Ma, F.-R., Sullivan, E. L., Munoz, O., Wood, C. R., Greenfield, E. A., Freeman, G. J. (2003). Blockade of Programmed Death-1 Ligands on Dendritic Cells Enhances T Cell Activation and Cytokine Production. J. Immunol. 170: 1257-1266 [Abstract] [Full Text]  
• Bennett, F., Luxenberg, D., Ling, V., Wang, I-M., Marquette, K., Lowe, D., Khan, N., Veldman, G., Jacobs, K. A., Valge-Archer, V. E., Collins, M., Carreno, B. M. (2003). Program Death-1 Engagement Upon TCR Activation Has Distinct Effects on Costimulation and Cytokine-Driven Proliferation: Attenuation of ICOS, IL-4, and IL-21, But Not CD28, IL-7, and IL-15 Responses. J. Immunol. 170: 711-718 [Abstract] [Full Text]  
• Ozkaynak, E., Wang, L., Goodearl, A., McDonald, K., Qin, S., O'Keefe, T., Duong, T., Smith, T., Gutierrez-Ramos, J.-C., Rottman, J. B., Coyle, A. J., Hancock, W. W. (2002). Programmed Death-1 Targeting Can Promote Allograft Survival. J. Immunol. 169: 6546-6553 [Abstract] [Full Text]  
• Nguyen, L. T., Radhakrishnan, S., Ciric, B., Tamada, K., Shin, T., Pardoll, D. M., Chen, L., Rodriguez, M., Pease, L. R. (2002). Cross-linking the B7 Family Molecule B7-DC Directly Activates Immune Functions of Dendritic Cells. JEM 196: 1393-1398 [Abstract] [Full Text]  
• Yamazaki, T., Akiba, H., Iwai, H., Matsuda, H., Aoki, M., Tanno, Y., Shin, T., Tsuchiya, H., Pardoll, D. M., Okumura, K., Azuma, M., Yagita, H. (2002). Expression of Programmed Death 1 Ligands by Murine T Cells and APC. J. Immunol. 169: 5538-5545 [Abstract] [Full Text]  
• Banerjee, P. P., Vinay, D. S., Mathew, A., Raje, M., Parekh, V., Prasad, D. V. R., Kumar, A., Mitra, D., Mishra, G. C. (2002). Evidence That Glycoprotein 96 (B2), a Stress Protein, Functions as a Th2-Specific Costimulatory Molecule. J. Immunol. 169: 3507-3518 [Abstract] [Full Text]  
• Prasad, D. V. R., Parekh, V. V., Joshi, B. N., Banerjee, P. P., Parab, P. B., Chattopadhyay, S., Kumar, A., Mishra, G. C. (2002). The Th1-Specific Costimulatory Molecule, M150, Is a Posttranslational Isoform of Lysosome-Associated Membrane Protein-1. J. Immunol. 169: 1801-1809 [Abstract] [Full Text]  
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• Wilcox, R. A., Chapoval, A. I., Gorski, K. S., Otsuji, M., Shin, T., Flies, D. B., Tamada, K., Mittler, R. S., Tsuchiya, H., Pardoll, D. M., Chen, L. (2002). Expression of Functional CD137 Receptor by Dendritic Cells. J. Immunol. 168: 4262-4267 [Abstract] [Full Text]  
• Cui, Y., Golob, J., Kelleher, E., Ye, Z., Pardoll, D., Cheng, L. (2002). Targeting transgene expression to antigen-presenting cells derived from lentivirus-transduced engrafting human hematopoietic stem/progenitor cells. Blood 99: 399-408 [Abstract] [Full Text]  
• Steinman, R. M., Nussenzweig, M. C. (2002). Avoiding horror autotoxicus: The importance of dendritic cells in peripheral T cell tolerance. Proc. Natl. Acad. Sci. USA 10.1073/pnas.231606698v1 [Abstract] [Full Text]  
• Deurloo, D. T., van Esch, B. C.A.M., Hofstra, C. L., Nijkamp, F. P., van Oosterhout, A. J.M. (2001). CTLA4-IgG Reverses Asthma Manifestations in a Mild but Not in a More ""Severe"" Ongoing Murine Model. Am. J. Respir. Cell Mol. Bio. 25: 751-760 [Abstract] [Full Text]  
• Liu, X., Bai, X.-F., Wen, J., Gao, J.-X., Liu, J., Lu, P., Wang, Y., Zheng, P., Liu, Y. (2001). B7H Costimulates Clonal Expansion of, and Cognate Destruction of Tumor Cells by, CD8+ T Lymphocytes In Vivo. JEM 194: 1339-1348 [Abstract] [Full Text]  
• Okazaki, T., Maeda, A., Nishimura, H., Kurosaki, T., Honjo, T. (2001). PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine. Proc. Natl. Acad. Sci. USA 10.1073/pnas.231486598v1 [Abstract] [Full Text]  
• Okazaki, T., Maeda, A., Nishimura, H., Kurosaki, T., Honjo, T. (2001). PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine. Proc. Natl. Acad. Sci. USA 98: 13866-13871 [Abstract] [Full Text]  
• Steinman, R. M., Nussenzweig, M. C. (2002). Inaugural Article: Avoiding horror autotoxicus: The importance of dendritic cells in peripheral T cell tolerance. Proc. Natl. Acad. Sci. USA 99: 351-358 [Abstract] [Full Text]  

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