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

doi:10.1084/jem.193.7.839

Published online 2 April 2001.

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© The Rockefeller University Press, 0022-1007/2001/4/839/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 7, April 2, 2001 839-846

Original Article

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

Su-Yi Tseng^a, Mizuto Otsuji^a, Kevin Gorski^a, Xin Huang^a, Jill E. Slansky^a, Sara I. Pai^a, Ahmed Shalabi^a, Tahiro Shin^a, Drew M. Pardoll^a, and Haruo Tsuchiya^a

^a Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Department of Oncology, Johns Hopkins School of Medicine, 1650 Orleans St.-1, CRB-Rm. 440, Baltimore, MD 21231.410-614-0549410-955-7866

dmpardol{at}jhmi.edu

Dendritic cells (DCs), unique antigen-presenting cells (APCs)with potent T cell stimulatory capacity, direct the activationand differentiation of T cells by providing costimulatory signals.As such, they are critical regulators of both natural and vaccine-inducedimmune responses. A new B7 family member, B7-DC, whose expressionis highly restricted to DCs, was identified among a libraryof genes differentially expressed between DCs and activatedmacrophages. B7-DC fails to bind the B7.1/2 receptors CD28 andcytotoxic T lymphocyte–associated antigen (CTLA)-4, butdoes bind PD-1, a receptor for B7-H1/PD-L1. B7-DC costimulatesT cell proliferation more efficiently than B7.1 and inducesa distinct pattern of lymphokine secretion. In particular, B7-DCstrongly costimulates interferon ${gamma}$ but not interleukin (IL)-4or IL-10 production from isolated naive T cells. These propertiesof B7-DC may account for some of the unique activity of DCs,such as their ability to initiate potent T helper cell type1 responses.

Key Words: dendritic cells • T cell activation • B7 • interferon ${gamma}$ • costimulatory molecule

S.-Y. Tseng, M. Otsuji, and K. Gorski contributed equally tothis work.

Abbreviations used in this paper: aa, amino acid(s); BAC, bacterialartificial chromosome; CTLA, CTL-associated antigen; DC, dendriticcell; HA, hemagglutinin; RACE, rapid amplification of cDNA ends;RT, reverse transcription.

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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]
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Sun, M., Richards, S., Prasad, D. V. R., Mai, X. M., Rudensky, A., Dong, C. (2002). Characterization of Mouse and Human B7-H3 Genes. J. Immunol. 168: 6294-6297 [Abstract] [Full Text]
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]
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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]