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Science 297 (5588): 1867-1870

Copyright © 2002 by the American Association for the Advancement of Science

Potential Regulatory Function of Human Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase

David H. Munn,12* Madhav D. Sharma,1 Jeffrey R. Lee,13 Kanchan G. Jhaver,1dagger Theodore S. Johnson,1 Derin B. Keskin,1 Brendan Marshall,1 Phillip Chandler,1 Scott J. Antonia,4 Russell Burgess,5 Craig L. Slingluff Jr.,6 Andrew L. Mellor15

Antigen-presenting cells (APCs) can induce tolerance or immunity. We describe a subset of human APCs that express indoleamine 2,3-dioxygenase (IDO) and inhibit T cell proliferation in vitro. IDO-positive APCs constituted a discrete subset identified by coexpression of the cell-surface markers CD123 and CCR6. In the dendritic cell (DC) lineage, IDO-mediated suppressor activity was present in fully mature as well as immature CD123+ DCs. IDO+ DCs could also be readily detected in vivo, which suggests that these cells may represent a regulatory subset of APCs in humans.

1 Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
2 Department of Pediatrics, Medical College of Georgia, Augusta, GA 30912, USA.
3 Veterans Affairs Medical Center, and Department of Pathology, Medical College of Georgia, Augusta, GA 30912, USA.
4 Interdisciplinary Oncology Program, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.
5 Department of Medicine, Medical College of Georgia, Augusta, GA 30912, USA.
6 Department of Surgery, University of Virginia, Charlottesville, VA 22908, USA.
*   To whom correspondence should be addressed. E-mail: dmunn{at}mail.mcg.edu

dagger    Current address: Lexicon Genetics, Inc., Woodlands, TX 77381, USA.



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Suppression of Memory CD8 T Cell Generation and Function by Tryptophan Catabolism.
Z. Liu, H. Dai, N. Wan, T. Wang, S. Bertera, M. Trucco, and Z. Dai (2007)
J. Immunol. 178, 4260-4266
   Abstract »    Full Text »    PDF »
Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells.
A. Curti, S. Pandolfi, B. Valzasina, M. Aluigi, A. Isidori, E. Ferri, V. Salvestrini, G. Bonanno, S. Rutella, I. Durelli, et al. (2007)
Blood 109, 2871-2877
   Abstract »    Full Text »    PDF »
Inhibition of Indoleamine 2,3-Dioxygenase in Dendritic Cells by Stereoisomers of 1-Methyl-Tryptophan Correlates with Antitumor Responses.
D.-Y. Hou, A. J. Muller, M. D. Sharma, J. DuHadaway, T. Banerjee, M. Johnson, A. L. Mellor, G. C. Prendergast, and D. H. Munn (2007)
Cancer Res. 67, 792-801
   Abstract »    Full Text »    PDF »
A putative mechanism on remission of multiple sclerosis during pregnancy: estrogen-induced indoleamine 2,3-dioxygenase by dendritic cells.
W-H Zhu, C-Z Lu, Y-M Huang, H Link, and B-G Xiao (2007)
Multiple Sclerosis Journal 13, 33-40
   Abstract »    PDF »
The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function.
M. D. Chiesa, S. Carlomagno, G. Frumento, M. Balsamo, C. Cantoni, R. Conte, L. Moretta, A. Moretta, and M. Vitale (2006)
Blood 108, 4118-4125
   Abstract »    Full Text »    PDF »
A high-affinity, tryptophan-selective amino acid transport system in human macrophages.
R. L. Seymour, V. Ganapathy, A. L. Mellor, and D. H. Munn (2006)
J. Leukoc. Biol. 80, 1320-1327
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IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features.
L. Gabriele, A. Fragale, P. Borghi, P. Sestili, E. Stellacci, M. Venditti, G. Schiavoni, M. Sanchez, F. Belardelli, and A. Battistini (2006)
J. Leukoc. Biol. 80, 1500-1511
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Synovial Autoreactive T Cells in Rheumatoid Arthritis Resist IDO-Mediated Inhibition.
L. Zhu, F. Ji, Y. Wang, Y. Zhang, Q. Liu, J. Z. Zhang, K. Matsushima, Q. Cao, and Y. Zhang (2006)
J. Immunol. 177, 8226-8233
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Cationic amino acid transporter 2 regulates inflammatory homeostasis in the lung.
M. E. Rothenberg, M. P. Doepker, I. P. Lewkowich, M. G. Chiaramonte, K. F. Stringer, F. D. Finkelman, C. L. MacLeod, L. G. Ellies, and N. Zimmermann (2006)
PNAS 103, 14895-14900
   Abstract »    Full Text »    PDF »
Thymosin {alpha}1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance.
L. Romani, F. Bistoni, K. Perruccio, C. Montagnoli, R. Gaziano, S. Bozza, P. Bonifazi, G. Bistoni, G. Rasi, A. Velardi, et al. (2006)
Blood 108, 2265-2274
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Adult stem cells in the treatment of autoimmune diseases.
J. M. van Laar and A. Tyndall (2006)
Rheumatology 45, 1187-1193
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Tolerogenic dendritic cells: cytokine modulation comes of age.
S. Rutella, S. Danese, and G. Leone (2006)
Blood 108, 1435-1440
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1-Methyl-Tryptophan Can Interfere with TLR Signaling in Dendritic Cells Independently of IDO Activity.
S. Agaugue, L. Perrin-Cocon, F. Coutant, P. Andre, and V. Lotteau (2006)
J. Immunol. 177, 2061-2071
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Endothelial stroma programs hematopoietic stem cells to differentiate into regulatory dendritic cells through IL-10.
H. Tang, Z. Guo, M. Zhang, J. Wang, G. Chen, and X. Cao (2006)
Blood 108, 1189-1197
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Update on Immunotherapy for Melanoma.
A. Ribas (2006)
J Natl Compr Canc Netw 4, 687-694
   Abstract »    PDF »
CTLA-4 Overexpression Inhibits T Cell Responses through a CD28-B7-Dependent Mechanism.
J. J. Engelhardt, T. J. Sullivan, and J. P. Allison (2006)
J. Immunol. 177, 1052-1061
   Abstract »    Full Text »    PDF »

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