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Potential Regulatory Function of Human Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase
David H. Munn,12*Madhav D. Sharma,1Jeffrey R. Lee,13Kanchan G. Jhaver,1Theodore S. Johnson,1Derin B. Keskin,1Brendan Marshall,1Phillip Chandler,1Scott J. Antonia,4Russell Burgess,5Craig L. Slingluff Jr.,6Andrew L. Mellor15
Antigen-presenting cells (APCs) can induce tolerance or
immunity. We describe a subset of human APCs that express indoleamine2,3-dioxygenase (IDO) and inhibit T cell proliferation in vitro.IDO-positive APCs constituted a discrete subset identified bycoexpression of the cell-surface markers CD123 and CCR6. In thedendritic cell (DC) lineage, IDO-mediated suppressor activitywas
present in fully mature as well as immature CD123+ DCs.
IDO+ DCs could also be readily detected in vivo, which
suggests thatthese 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
Current address: Lexicon Genetics, Inc., Woodlands, TX
77381, USA.
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C. Dercamp, K. Chemin, C. Caux, G. Trinchieri, and A. P. Vicari (2005)
Cancer Res.
65, 8479-8486
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Early Cytokine Production Is Associated with Protection from Murine Cerebral Malaria.
A. J. Mitchell, A. M. Hansen, L. Hee, H. J. Ball, S. M. Potter, J. C. Walker, and N. H. Hunt (2005)
Infect. Immun.
73, 5645-5653
|Abstract »|Full Text »|PDF »
Profiling dendritic cell maturation with dedicated microarrays.
D. McIlroy, S. Tanguy-Royer, N. Le Meur, I. Guisle, P.-J. Royer, J. Leger, K. Meflah, and M. Gregoire (2005)
J. Leukoc. Biol.
78, 794-803
|Abstract »|Full Text »|PDF »
Indoleamine 2,3-Dioxygenase Serves as a Marker of Poor Prognosis in Gene Expression Profiles of Serous Ovarian Cancer Cells.
A. Okamoto, T. Nikaido, K. Ochiai, S. Takakura, M. Saito, Y. Aoki, N. Ishii, N. Yanaihara, K. Yamada, O. Takikawa, et al. (2005)
Clin. Cancer Res.
11, 6030-6039
|Abstract »|Full Text »|PDF »
Blockade of B7-H1 on Macrophages Suppresses CD4+ T Cell Proliferation by Augmenting IFN-{gamma}-Induced Nitric Oxide Production.
T. Yamazaki, H. Akiba, A. Koyanagi, M. Azuma, H. Yagita, and K. Okumura (2005)
J. Immunol.
175, 1586-1592
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A minor population of splenic dendritic cells expressing CD19 mediates IDO-dependent T cell suppression via type I IFN signaling following B7 ligation.
B. Baban, A. M. Hansen, P. R. Chandler, A. Manlapat, A. Bingaman, D. J. Kahler, D. H. Munn, and A. L. Mellor (2005)
Int. Immunol.
17, 909-919
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Monocyte-mediated T-cell suppression and augmented monocyte tryptophan catabolism after human hematopoietic stem-cell transplantation.
U. Hainz, P. Obexer, C. Winkler, P. Sedlmayr, O. Takikawa, H. Greinix, A. Lawitschka, U. Putschger, D. Fuchs, S. Ladisch, et al. (2005)
Blood
105, 4127-4134
|Abstract »|Full Text »|PDF »
Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells.
S. Glennie, I. Soeiro, P. J. Dyson, E. W.-F. Lam, and F. Dazzi (2005)
Blood
105, 2821-2827
|Abstract »|Full Text »|PDF »
CCR6 expression defines regulatory effector/memory-like cells within the CD25+CD4+ T-cell subset.
M. Kleinewietfeld, F. Puentes, G. Borsellino, L. Battistini, O. Rotzschke, and K. Falk (2005)
Blood
105, 2877-2886
|Abstract »|Full Text »|PDF »
Dendritic cells have the option to express IDO-mediated suppression or not.
D. H. Munn, A. L. Mellor, M. Rossi, and J. W. Young (2005)
Blood
105, 2618
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Regulation of human auto- and alloreactive T cells by indoleamine 2,3-dioxygenase (IDO)-producing dendritic cells: too much ado about IDO?.
P. Terness, J.-J. Chuang, T. Bauer, L. Jiga, and G. Opelz (2005)
Blood
105, 2480-2486
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A Crucial Role for Tryptophan Catabolism at the Host/Candida albicans Interface.
S. Bozza, F. Fallarino, L. Pitzurra, T. Zelante, C. Montagnoli, S. Bellocchio, P. Mosci, C. Vacca, P. Puccetti, and L. Romani (2005)
J. Immunol.
174, 2910-2918
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Intercellular Adhesion Molecule-1/LFA-1 Cross Talk Is a Proximate Mediator Capable of Disrupting Immune Integration and Tolerance Mechanism at the Feto-Maternal Interface in Murine Pregnancies.
S. Blois, M. Tometten, J. Kandil, E. Hagen, B. F. Klapp, R. A. Margni, and P. C. Arck (2005)
J. Immunol.
174, 1820-1829
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Regulation of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA-synthetase by CTLA-4-Fc in human CD4+ T cells.
A. Boasso, J.-P. Herbeuval, A. W. Hardy, C. Winkler, and G. M. Shearer (2005)
Blood
105, 1574-1581
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Quantitative Analysis of Melanoma-Induced Cytokine-Mediated Immunosuppression in Melanoma Sentinel Nodes.
J. H. Lee, H. Torisu-Itakara, A. J. Cochran, A. Kadison, Y. Huynh, D. L. Morton, and R. Essner (2005)
Clin. Cancer Res.
11, 107-112
|Abstract »|Full Text »|PDF »
Mechanisms regulating the expression of indoleamine 2,3-dioxygenase during decidualization of human endometrium.
A. Honig, L. Rieger, J. Dietl, and U. Kammerer (2004)
Hum. Reprod.
19, 2683-2684
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Manipulating dendritic cell biology for the active immunotherapy of cancer.
Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase.
A. L. Mellor, P. Chandler, B. Baban, A. M. Hansen, B. Marshall, J. Pihkala, H. Waldmann, S. Cobbold, E. Adams, and D. H. Munn (2004)
Int. Immunol.
16, 1391-1401
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In Reply:.
C. L. Slingluff Jr (2004)
J. Clin. Oncol.
22, 3835
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