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* Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan;
Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan; and
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231
Programmed death 1 (PD-1) is a new member of the CD28/CTLA-4
family, which has been implicated in the maintenance of peripheral
tolerance. Two ligands for PD-1, namely, B7-H1 (PD-L1) and B7-DC
(PD-L2), have recently been identified as new members of the B7 family
but their expression at the protein level remains largely unknown. To
characterize the expression of B7-H1 and B7-DC, we newly generated an
anti-mouse B7-H1 mAb (MIH6) and an anti-mouse B7-DC mAb (TY25).
MIH6 and TY25 immunoprecipitated a single molecule of 43 and 42 kDa
from the lysate of B7-H1 and B7-DC transfectants, respectively. Flow
cytometric analysis revealed that B7-H1 was broadly expressed on the
surface of mouse tumor cell lines while the expression of B7-DC was
rather restricted. PD-1 was expressed on anti-CD3-stimulated T
cells and anti-IgM plus anti-CD40-stimulated B cells at high
levels but was undetectable on activated macrophages or DCs. B7-H1 was
constitutively expressed on freshly isolated splenic T cells, B cells,
macrophages, and dendritic cells (DCs), and up-regulated on T cells by
anti-CD3 stimulation on macrophages by LPS, IFN-
, GM-CSF, or
IL-4, and on DCs by IFN-, GM-CSF, or IL-4. In contrast, B7-DC
expression was only inducible on macrophages and DCs upon stimulation
with IFN-, GM-CSF, or IL-4. The inducible expression of PD-1 ligands
on both T cells and APCs may suggest new paradigms of PD-1-mediated
immune regulation.
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Y.-F. He, G.-M. Zhang, X.-H. Wang, H. Zhang, Y. Yuan, D. Li, and Z.-H. Feng Blocking Programmed Death-1 Ligand-PD-1 Interactions by Local Gene Therapy Results in Enhancement of Antitumor Effect of Secondary Lymphoid Tissue Chemokine J. Immunol., October 15, 2004; 173(8): 4919 - 4928. [Abstract] [Full Text] [PDF]
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A. Saudemont and B. Quesnel In a model of tumor dormancy, long-term persistent leukemic cells have increased B7-H1 and B7.1 expression and resist CTL-mediated lysis Blood, October 1, 2004; 104(7): 2124 - 2133. [Abstract] [Full Text] [PDF]
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X. Zhong, C. Bai, W. Gao, T. B. Strom, and T. L. Rothstein Suppression of expression and function of negative immune regulator PD-1 by certain pattern recognition and cytokine receptor signals associated with immune system danger Int. Immunol., August 1, 2004; 16(8): 1181 - 1188. [Abstract] [Full Text] [PDF]
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Y. E. Latchman, S. C. Liang, Y. Wu, T. Chernova, R. A. Sobel, M. Klemm, V. K. Kuchroo, G. J. Freeman, and A. H. Sharpe PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells PNAS, July 20, 2004; 101(29): 10691 - 10696. [Abstract] [Full Text] [PDF]
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S. Radhakrishnan, L. T. Nguyen, B. Ciric, D. Flies, V. P. V. Keulen, K. Tamada, L. Chen, M. Rodriguez, and L. R. Pease Immunotherapeutic Potential of B7-DC (PD-L2) Cross-Linking Antibody In Conferring Antitumor Immunity Cancer Res., July 15, 2004; 64(14): 4965 - 4972. [Abstract] [Full Text] [PDF]
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P. Smith, C. M. Walsh, N. E. Mangan, R. E. Fallon, J. R. Sayers, A. N. J. McKenzie, and P. G. Fallon Schistosoma mansoni Worms Induce Anergy of T Cells via Selective Up-Regulation of Programmed Death Ligand 1 on Macrophages J. Immunol., July 15, 2004; 173(2): 1240 - 1248. [Abstract] [Full Text] [PDF]
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M. Y. Balkhi, V. K. Latchumanan, B. Singh, P. Sharma, and K. Natarajan Cross-regulation of CD86 by CD80 differentially regulates T helper responses from Mycobacterium tuberculosis secretory antigen-activated dendritic cell subsets J. Leukoc. Biol., May 1, 2004; 75(5): 874 - 883. [Abstract] [Full Text] [PDF]
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M. A. Holsti, T. Chitnis, R. J. Panzo, R. T. Bronson, H. Yagita, M. H. Sayegh, and A. O. Tzianabos Regulation of Postsurgical Fibrosis by the Programmed Death-1 Inhibitory Pathway J. Immunol., May 1, 2004; 172(9): 5774 - 5781. [Abstract] [Full Text] [PDF]
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K. Matsumoto, H. Inoue, T. Nakano, M. Tsuda, Y. Yoshiura, S. Fukuyama, F. Tsushima, T. Hoshino, H. Aizawa, H. Akiba, et al. B7-DC Regulates Asthmatic Response by an IFN-{gamma}-Dependent Mechanism J. Immunol., February 15, 2004; 172(4): 2530 - 2541. [Abstract] [Full Text] [PDF]
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C. Blank, I. Brown, A. C. Peterson, M. Spiotto, Y. Iwai, T. Honjo, and T. F. Gajewski PD-L1/B7H-1 Inhibits the Effector Phase of Tumor Rejection by T Cell Receptor (TCR) Transgenic CD8+ T Cells Cancer Res., February 1, 2004; 64(3): 1140 - 1145. [Abstract] [Full Text] [PDF]
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I. Lee, L. Wang, A. D. Wells, Q. Ye, R. Han, M. E. Dorf, W. A. Kuziel, B. J. Rollins, L. Chen, and W. W. Hancock Blocking the Monocyte Chemoattractant Protein-1/CCR2 Chemokine Pathway Induces Permanent Survival of Islet Allografts through a Programmed Death-1 Ligand-1-Dependent Mechanism J. Immunol., December 15, 2003; 171(12): 6929 - 6935. [Abstract] [Full Text] [PDF]
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T. Kanai, T. Totsuka, K. Uraushihara, S. Makita, T. Nakamura, K. Koganei, T. Fukushima, H. Akiba, H. Yagita, K. Okumura, et al. Blockade of B7-H1 Suppresses the Development of Chronic Intestinal Inflammation J. Immunol., October 15, 2003; 171(8): 4156 - 4163. [Abstract] [Full Text] [PDF]
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T. Shin, G. Kennedy, K. Gorski, H. Tsuchiya, H. Koseki, M. Azuma, H. Yagita, L. Chen, J. Powell, D. Pardoll, et al. Cooperative B7-1/2 (CD80/CD86) and B7-DC Costimulation of CD4+ T Cells Independent of the PD-1 Receptor J. Exp. Med., July 7, 2003; 198(1): 31 - 38. [Abstract] [Full Text] [PDF]
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Y. Iwai, S. Terawaki, M. Ikegawa, T. Okazaki, and T. Honjo PD-1 Inhibits Antiviral Immunity at the Effector Phase in the Liver J. Exp. Med., July 7, 2003; 198(1): 39 - 50. [Abstract] [Full Text] [PDF]
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M. J. I. Ansari, A. D. Salama, T. Chitnis, R. N. Smith, H. Yagita, H. Akiba, T. Yamazaki, M. Azuma, H. Iwai, S. J. Khoury, et al. The Programmed Death-1 (PD-1) Pathway Regulates Autoimmune Diabetes in Nonobese Diabetic (NOD) Mice J. Exp. Med., July 7, 2003; 198(1): 63 - 69. [Abstract] [Full Text] [PDF]
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A. D. Salama, T. Chitnis, J. Imitola, M. J. I. Ansari, H. Akiba, F. Tushima, M. Azuma, H. Yagita, M. H. Sayegh, and S. J. Khoury Critical Role of the Programmed Death-1 (PD-1) Pathway in Regulation of Experimental Autoimmune Encephalomyelitis J. Exp. Med., July 7, 2003; 198(1): 71 - 78. [Abstract] [Full Text] [PDF]
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P'n. Loke and J. P. Allison PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells PNAS, April 29, 2003; 100(9): 5336 - 5341. [Abstract] [Full Text] [PDF]
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