Ido expression by dendritic cells: tolerance and tryptophan catabolism (original) (raw)

• Uhlig, H. H. & Powrie, F. Dendritic cells and the intestinal bacterial flora: a role for localized mucosal immune responses. J. Clin. Invest. 112, 648–651 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Sotomayor, E. M. et al. Cross-presentation of tumor antigens by bone marrow-derived antigen-presenting cells is the dominant mechanism in the induction of T-cell tolerance during B-cell lymphoma progression. Blood 98, 1070–1077 (2001).
  Article CAS PubMed Google Scholar
• Moser, M. Dendritic cells in immunity and tolerance — do they display opposite functions? Immunity 19, 5–8 (2003).
  Article CAS PubMed Google Scholar
• Hackstein, H. & Thomson, A. W. Dendritic cells: emerging pharmacological targets of immunosuppressive drugs. Nature Rev. Immunol. 4, 24–34 (2004).
  Article CAS Google Scholar
• Mosmann, T. R. & Livingstone, A. M. Dendritic cells: the immune information management experts. Nature Immunol. 5, 564–566 (2004).
  Article CAS Google Scholar
• Bendelac, A. & Medzhitov, R. Adjuvants of immunity: harnessing innate immunity to promote adaptive immunity. J. Exp. Med. 195, F19–F23 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Steinman, R. M., Hawiger, D. & Nussenzweig, M. C. Tolerogenic dendritic cells. Annu. Rev. Immunol. 21, 685–711 (2003).
  Article CAS PubMed Google Scholar
• Medzhitov, R. & Janeway, C. A., Jr. Decoding the patterns of self and nonself by the innate immune system. Science 296, 298–300 (2002).
  Article CAS PubMed Google Scholar
• Probst, H. C., Lagnel, J., Kollias, G. & van den Broek, M. Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Immunity 18, 713–720 (2003).
  Article CAS PubMed Google Scholar
• Bonifaz, L. et al. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J. Exp. Med. 196, 1627–1638 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Chen, W., Frank, M. E., Jin, W. & Wahl, S. M. TGF-β released by apoptotic T cells contributes to an immunosuppressive milieu. Immunity 14, 715–725 (2001).
  Article CAS PubMed Google Scholar
• Powrie, F. & Maloy, K. J. Immunology. Regulating the regulators. Science 299, 1030–1031 (2003).
  Article CAS PubMed Google Scholar
• Fairchild, P. J. & Waldmann, H. Dendritic cells and prospects for transplantation tolerance. Curr. Opin. Immunol. 12, 528–535 (2000).
  Article CAS PubMed Google Scholar
• Taylor, M. W. & Feng, G. Relationship between interferon-γ, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J. 5, 2516–2522 (1991).
  Article CAS PubMed Google Scholar
• Mellor, A. L. & Munn, D. H. Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol. Today 20, 469–473 (1999).
  Article CAS PubMed Google Scholar
• Munn, D. H. et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 281, 1191–1193 (1998). This report shows that IDO activity inhibits a T-cell-mediated process in mice; in this case maternal T-cell immunity to fetal alloantigens during pregnancy.
  Article CAS PubMed Google Scholar
• Mellor, A. L., Keskin, D. B., Johnson, T., Chandler, P. & Munn, D. H. Cells expressing indoleamine 2,3 dioxygenase inhibit T cell responses. J. Immunol. 168, 3771–3776 (2002).
  Article CAS PubMed Google Scholar
• Friberg, M. et al. Indoleamine 2,3-dioxygenase contributes to tumor cell evasion of T cell-mediated rejection. Int. J. Cancer 101, 151–155 (2002). References 18 and 19 show that IDO activity can suppress antitumour immunity, challenging previous notions that IDO activity is exclusively an innate host defence mechanism against tumours.
  Article CAS PubMed Google Scholar
• Uyttenhove, C. et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nature Med. 9, 1269–1274 (2003).
  Article CAS PubMed Google Scholar
• Munn, D. H. et al. Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J. Clin. Invest. 114, 280–290 (2004). This report identifies specific DC subsets in mice that express IDO, accumulate in tumour-draining lymph nodes and mediate potent T-cell suppression.
  Article CAS PubMed PubMed Central Google Scholar
• Grohmann, U. et al. A defect in tryptophan catabolism impairs tolerance in nonobese diabetic mice. J. Exp. Med. 198, 153–160 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Grohmann, U. et al. CTLA-4–Ig regulates tryptophan catabolism in vivo. Nature Immunol. 3, 1097–1101 (2002). This paper indicates that ligation of CD80/CD86 is an alternative mechanism to induce functional IDO-expression by mouse DCs and showed that a component of CTLA4–immunoglobulin-mediated inhibition of allograft rejection was IDO dependent.
  Article CAS Google Scholar
• Sakurai, K., Zou, J., Tschetter, J., Ward, J. & Shearer, G. Effect of indoleamine 2,3-dioxygenase on induction of experimental autoimmune encephalomyelitis. J. Neuroimmunol. 129, 186–196 (2002).
  Article CAS PubMed Google Scholar
• Gurtner, G. J., Newberry, R. D., Schloemann, S. R., McDonald, K. G. & Stenson, W. F. Inhibition of indoleamine 2,3-dioxygenase augments trinitrobenzene sulfonic acid colitis in mice. Gastroenterology 125, 1762–1773 (2003).
  Article CAS PubMed Google Scholar
• Swanson, K. A., Zheng, Y., Heidler, K. M., Mizobuchi, T. & Wilkes, D. S. CD11c+ cells modulate pulmonary immune responses by production of indoleamine 2,3-dioxygenase. Am. J. Respir. Cell Mol. Biol. 30, 311–318 (2004).
  Article CAS PubMed Google Scholar
• Hayashi, T. et al. Inhibition of experimental asthma by indoleamine 2,3-dioxygenase. J. Clin. Invest. 114, 270–279 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Grohmann, U., Fallarino, F. & Puccetti, P. Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol. 24, 242–248 (2003).
  Article CAS PubMed Google Scholar
• Stone, T. W. & Darlington, L. G. Endogenous kynurenines as targets for drug discovery and development. Nature Rev. Drug Discov. 1, 609–620 (2002).
  Article CAS Google Scholar
• Suzuki, T. et al. Comparison of the sequences of Turbo and Sulculus indoleamine dioxygenase-like myoglobin genes. Gene 308, 89–94 (2003).
  Article CAS PubMed Google Scholar
• Dai, W. & Gupta, S. L. Regulation of indoleamine 2,3-dioxygenase gene expression in human fibroblasts by interferon-γ. J. Biol. Chem. 265, 19871–19877 (1990).
  CAS PubMed Google Scholar
• Hassanain, H. H., Chon, S. Y. & Gupta, S. L. Differential regulation of human indoleamine 2,3-dioxygenase gene expression by interferons-γ and -α. Analysis of the regulatory region of the gene and identification of an interferon-γ-inducible DNA-binding factor. J. Biol. Chem. 268, 5077–5084 (1993).
  CAS PubMed Google Scholar
• Burke, F., Knowles, R. G., East, N. & Balkwill, F. R. The role of indoleamine 2,3-dioxygenase in the anti-tumour activity of human interferon-γ in vivo. Int. J. Cancer 60, 115–122 (1995).
  Article CAS PubMed Google Scholar
• Varga, J., Yufit, T., Hitraya, E. & Brown, R. R. Control of extracellular matrix degradation by interferon-γ. The tryptophan connection. Adv. Exp. Med. Biol. 398, 143–148 (1996).
  Article CAS PubMed Google Scholar
• Munn, D. H. et al. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J. Exp. Med. 189, 1363–1372 (1999). This report identifies tryptophan depletion due to IDO upregulation in human macrophages as a mechanism to inhibit T cell proliferation.
  Article CAS PubMed PubMed Central Google Scholar
• Hwu, P. et al. Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J. Immunol. 164, 3596–3599 (2000). These authors show that human DCs also mediate IDO-dependent T-cell suppression.
  Article CAS PubMed Google Scholar
• Chon, S. Y., Hassanain, H. H. & Gupta, S. L. Cooperative role of interferon regulatory factor 1 and p91 (STAT1) response elements in intereron-γ-inducible expression of human indoleamine 2,3-dioxygenase gene. J. Biol. Chem. 271, 17247–17252 (1996).
  Article CAS PubMed Google Scholar
• Silva, N. M. et al. Expression of indoleamine 2,3-dioxygenase, tryptophan degradation, and kynurenine formation during in vivo infection with Toxoplasma gondii: induction by endogenous γ interferon and requirement of interferon regulatory factor 1. Infect. Immun. 70, 859–868 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Babcock, T. A. & Carlin, J. M. Transcriptional activation of indoleamine dioxygenase by interleukin 1 and tumor necrosis factor α in interferon-treated epithelial cells. Cytokine 12, 588–594 (2000).
  Article CAS PubMed Google Scholar
• Robinson, C. M., Shirey, K. A. & Carlin, J. M. Synergistic transcriptional activation of indoleamine dioxygenase by IFN-γ and tumor necrosis factor-α. J. Interferon Cytokine Res. 23, 413–421 (2003).
  Article CAS PubMed Google Scholar
• Fujigaki, S. et al. Lipopolysaccharide induction of indoleamine 2,3-dioxygenase is mediated dominantly by an IFN-γ-independent mechanism. Eur. J. Immunol. 31, 2313–2318 (2001).
  Article CAS PubMed Google Scholar
• Yuan, W., Collado-Hidalgo, A., Yufit, T., Taylor, M. & Varga, J. Modulation of cellular tryptophan metabolism in human fibroblasts by transforming growth factor-β: selective inhibition of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA synthetase gene expression. J. Cell. Physiol. 177, 174–186 (1998).
  Article CAS PubMed Google Scholar
• MacKenzie, C. R., Gonzalez, R. G., Kniep, E., Roch, S. & Daubener, W. Cytokine mediated regulation of interferon-γ-induced IDO activation. Adv. Exp. Med. Biol. 467, 533–539 (1999).
  Article CAS PubMed Google Scholar
• Fallarino, F. et al. Modulation of tryptophan catabolism by regulatory T cells. Nature Immunol. 4, 1206–1212 (2003). This report shows that T cells expressing CTLA4 induce IDO expression by DCs.
  Article CAS Google Scholar
• Mellor, A. L. et al. Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. J. Immunol. 171, 1652–1655 (2003). This paper shows that specific DC subsets in mouse spleens mediate dominant IDO-dependent T-cell suppression in vivo following ligation of CD80/CD86.
  Article CAS PubMed Google Scholar
• Munn, D. H., Sharma, M. D. & Mellor, A. L. Ligation of B7-1/B7-2 by human CD4+ T cells triggers indoleamine 2,3-dioxygenase activity in dendritic cells. J. Immunol. 172, 4100–4110 (2004).
  Article CAS PubMed Google Scholar
• Mellor, A. L. et al. Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase. Int. Immunol. (doi:10.93/intimm/dxh140). In this report, the T-cell-regulatory functions of certain cloned CD4+CD25+ T cells are shown to depend on their ability to induce functional IDO expression by specific DC subsets from mouse spleens through CD80/CD86 ligation.
• Finger, E. B. & Bluestone, J. A. When ligand becomes receptor — tolerance via B7 signaling on DCs. Nature Immunol. 3, 1056–1057 (2002).
  Article CAS Google Scholar
• Kudo, Y., Boyd, C. A., Sargent, I. L. & Redman, C. W. Tryptophan degradation by human placental indoleamine 2,3-dioxygenase regulates lymphocyte proliferation. J. Physiol. 535, 207–215 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Kudo, Y. & Boyd, C. A. Human placental indoleamine 2,3-dioxygenase: cellular localization and characterization of an enzyme preventing fetal rejection. Biochim. Biophys. Acta 1500, 119–124 (2000).
  Article CAS PubMed Google Scholar
• Kudo, Y. et al. Indoleamine 2,3-dioxygenase: distribution and function in the developing human placenta. J. Reprod. Immunol. 61, 87–98 (2004).
  Article CAS PubMed Google Scholar
• Honig, A. et al. Indoleamine 2,3-dioxygenase (IDO) expression in invasive extravillous trophoblast supports role of the enzyme for materno–fetal tolerance. J. Reprod. Immunol. 61, 79–86 (2004).
  Article CAS PubMed Google Scholar
• Baban, B. et al. Indoleamine 2,3-dioxygenase expression is restricted to fetal trophoblast giant cells during murine gestation and is maternal genome specific. J. Reprod. Immunol. 61, 67–77 (2004).
  Article CAS PubMed Google Scholar
• Mackler, A. M., Barber, E. M., Takikawa, O. & Pollard, J. W. Indoleamine 2,3-dioxygenase is regulated by IFN-γ in the mouse placenta during Listeria monocytogenes infection. J. Immunol. 170, 823–830 (2003).
  Article CAS PubMed Google Scholar
• Takikawa, O., Yoshida, R., Kido, R. & Hayaishi, O. Tryptophan degradation in mice initiated by indoleamine 2,3-dioxygenase. J. Biol. Chem. 261, 3648–3653 (1986).
  CAS PubMed Google Scholar
• Yoshida, R. et al. Regulation of indoleamine 2,3-dioxygenase activity in the small intestine and the epididymis of mice. Arch. Biochem. Biophys. 203, 343–351 (1980).
  Article CAS PubMed Google Scholar
• Yoshida, R., Urade, Y., Nakata, K., Watanabe, Y. & Hayashi, O. Specific induction of indoleamine 2,3-dioxygenase by bacterial lipopolysaccharide in the mouse lung. Arch. Biochem. Biophys. 212, 629–637 (1981).
  Article CAS PubMed Google Scholar
• Fallarino, F. et al. Functional expression of indoleamine 2,3-dioxygenase by murine CD8α+ dendritic cells. Int. Immunol. 14, 65–68 (2002).
  Article CAS PubMed Google Scholar
• Thomas, S. R. et al. Antioxidants inhibit indoleamine 2,3-dioxygenase in IFN-γ-activated human macrophages: posttranslational regulation by pyrrolidine dithiocarbamate. J. Immunol. 166, 6332–6340 (2001).
  Article CAS PubMed Google Scholar
• Aitken, J. B. et al. Determination of the nature of the heme environment in nitrosyl indoleamine 2,3-dioxygenase using multiple-scattering analyses of X-ray absorption fine structure. Biochemistry 43, 4892–4898 (2004).
  Article CAS PubMed Google Scholar
• Hucke, C., Mackenzie, C. R., Adjogble, K. D. Z., Takikawa, O. & Daubener, W. Nitric oxide-mediated regulation of γ-interferon-induced bacteriosis: inhibition of degradation of human indoleamine 2,3-dioxygenase. Infect. Immun. 72, 2723–2730 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Pfefferkorn, E. R. Interferon-γ blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan. Proc. Natl Acad. Sci. USA 81, 908–912 (1984).
  Article CAS PubMed PubMed Central Google Scholar
• Carlin, J. M., Borden, E. C., Sondel, P. M. & Byrne, G. I. Interferon-induced indoleamine 2,3-dioxygenase activity in human mononuclear phagocytes. J. Leukoc. Biol. 45, 29–34 (1989).
  Article CAS PubMed Google Scholar
• Gupta, S. L. et al. Antiparasitic and antiproliferative effects of indoleamine 2,3-dioxygenase enzyme expression in human fibroblasts. Infect. Immun. 62, 2277–2284 (1994).
  CAS PubMed PubMed Central Google Scholar
• MacKenzie, C. R., Hadding, U. & Daubener, W. Interferon-γ-induced activation of indoleamine 2,3-dioxygenase in cord blood monocyte-derived macrophages inhibits the growth of group B streptococci. J. Infect. Dis. 178, 875–878 (1998).
  Article CAS PubMed Google Scholar
• Hayashi, T. et al. Enhancement of innate immunity against Mycobacterium avium infection by immunostimulatory DNA is mediated by indoleamine 2,3-dioxygenase. Infect. Immun. 69, 6156–6164 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Bodaghi, B. et al. Role of IFN-γ-induced indoleamine 2,3 dioxygenase and inducible nitric oxide synthase in the replication of human cytomegalovirus in retinal pigment epithelial cells. J. Immunol. 162, 957–964 (1999).
  CAS PubMed Google Scholar
• Adams, O. et al. Role of indoleamine-2,3-dioxygenase in α/β and γ-interferon-mediated antiviral effects against herpes simplex virus infections. J. Virol. 78, 2632–2636 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Fujigaki, S. et al. L-tryptophan-L-kynurenine pathway metabolism accelerated by Toxoplasma gondii infection is abolished in γ-interferon-gene-deficient mice: cross-regulation between inducible nitric oxide synthase and indoleamine-2,3-dioxygenase. Infect. Immun. 70, 779–786 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Rottenberg, M. E. et al. Regulation and role of IFN-γ in the innate resistance to infection with Chlamydia pneumoniae. J. Immunol. 164, 4812–4818 (2000).
  Article CAS PubMed Google Scholar
• Widner, B., Weiss, G. & Fuchs, D. Tryptophan degradation to control T-cell responsiveness. Immunol. Today 21, 250 (2000).
  Article CAS PubMed Google Scholar
• Rogers, K. A. et al. Type 1 and type 2 responses to Leishmania major. FEMS Microbiol. Lett. 209, 1–7 (2002).
  Article CAS PubMed Google Scholar
• Cady, S. G. & Sono, M. 1-methyl-DL-tryptophan, β-(3-benzofuranyl)-DL-alanine (the oxygen analog of tryptophan), and β-[3-benzo(b)thienyl]-DL-alanine (the sulfur analog of tryptophan) are competitive inhibitors for indoleamine 2,3-dioxygenase. Arch. Biochem. Biophys. 291, 326–333 (1991).
  Article CAS PubMed Google Scholar
• Mellor, A. L. et al. Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nature Immunol. 2, 64–68 (2001).
  Article CAS Google Scholar
• Alexander, A. M. et al. Indoleamine 2,3-dioxygenase expression in transplanted NOD islets prolongs graft survival after adoptive transfer of diabetogenic splenocytes. Diabetes 51, 356–365 (2002).
  Article CAS PubMed Google Scholar
• Munn, D. H. et al. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 297, 1867–1870 (2002).
  Article CAS PubMed Google Scholar
• Summers, K. L., Hock, B. D., McKenzie, J. L. & Hart, D. N. Phenotypic characterization of five dendritic cell subsets in human tonsils. Am. J. Pathol. 159, 285–295 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Rissoan, M. C. et al. Subtractive hybridization reveals the expression of immunoglobulin-like transcript 7, Eph-B1, granzyme B, and 3 novel transcripts in human plasmacytoid dendritic cells. Blood 100, 3295–3303 (2002).
  Article CAS PubMed Google Scholar
• Grohmann, U. et al. IFN-γ inhibits presentation of a tumor/self peptide by CD8α− dendritic cells via potentiation of the CD8α+ subset. J. Immunol. 165, 1357–1363 (2000). This report identifies IDO as a mechanism used by mouse regulatory DCs.
  Article CAS PubMed Google Scholar
• Grohmann, U. et al. CD40 ligation ablates the tolerogenic potential of lymphoid dendritic cells. J. Immunol. 166, 277–283 (2001).
  Article CAS PubMed Google Scholar
• Grohmann, U. et al. IL-6 inhibits the tolerogenic function of CD8α+ dendritic cells expressing indoleamine 2,3-dioxygenase. J. Immunol. 167, 708–714 (2001).
  Article CAS PubMed Google Scholar
• Grohmann, U. et al. Functional plasticity of dendritic cell subsets as mediated by CD40 versus B7 activation. J. Immunol. 171, 2581–2587 (2003). This report shows that IDO-mediated suppression can be upregulated or downregulated by signals from the immune system.
  Article CAS PubMed Google Scholar
• O'Keeffe, M. et al. Mouse plasmacytoid cells: long-lived cells, heterogeneous in surface phenotype and function, that differentiate into CD8+ dendritic cells only after microbial stimulus. J. Exp. Med. 196, 1307–1319 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Martin, P. et al. Characterization of a new subpopulation of mouse CD8α+ B220+ dendritic cells endowed with type 1 interferon production capacity and tolerogenic potential. Blood 100, 383–390 (2002).
  Article CAS PubMed Google Scholar
• Aluvihare, V. R., Kallikourdis, M. & Betz, A. G. Regulatory T cells mediate maternal tolerance to the fetus. Nature Immunol. 5, 266–271 (2004).
  Article CAS Google Scholar
• Barcelo-Batllori, S. et al. Proteomic analysis of cytokine induced proteins in human intestinal epithelial cells: implications for inflammatory bowel diseases. Proteomics 2, 551–560 (2002).
  Article CAS PubMed Google Scholar
• Varga, J., Yufit, T. & Brown, R. R. Inhibition of collagenase and stromelysin gene expression by interferon-γ in human dermal fibroblasts is mediated in part via induction of tryptophan degradation. J. Clin. Invest. 96, 475–481 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Meisel, R. et al. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 103, 4619–4621 (2004).
  Article CAS PubMed Google Scholar
• von Bubnoff, D. et al. FcεRI induces the tryptophan degradation pathway involved in regulating T cell responses. J. Immunol. 169, 1810–1816 (2002).
  Article CAS PubMed Google Scholar
• Lee, G. K. et al. Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division. Immunology 107, 452–460 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Fallarino, F. et al. T cell apoptosis by tryptophan catabolism. Cell Death Differ. 9, 1069–1077 (2002). This report indicates that certain T cells are sensitive to the toxic effects of tryptophan metabolites that can be produced by cells expressing IDO.
  Article CAS PubMed Google Scholar
• Frumento, G. et al. Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. J. Exp. Med. 196, 459–468 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Terness, P. et al. Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J. Exp. Med. 196, 447–457 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Seman, M. et al. NAD-induced T cell death: ADP-ribosylation of cell surface proteins by ART2 activates the cytolytic P2X7 purinoceptor. Immunity 19, 571–582 (2003).
  Article CAS PubMed Google Scholar
• Moffett, J. R. & Namboodiri, M. A. Tryptophan and the immune response. Immunol. Cell Biol. 81, 247–265 (2003).
  Article CAS PubMed Google Scholar
• Zhang, P. et al. The GCN2 eIF2α kinase is required for adaptation to amino acid deprivation in mice. Mol. Cell. Biol. 22, 6681–6688 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Harding, H. P. et al. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol. Cell 6, 1099–1108 (2000).
  Article CAS PubMed Google Scholar
• Rohde, J., Heitman, J. & Cardenas, M. E. The TOR kinases link nutrient sensing to cell growth. J. Biol. Chem. 276, 9583–9586 (2001).
  Article CAS PubMed Google Scholar
• Gao, X. et al. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nature Cell Biol. 4, 699–704 (2002).
  Article CAS PubMed Google Scholar
• Marshall, B., Keskin, D. B. & Mellor, A. L. Regulation of prostaglandin synthesis and cell adhesion by a tryptophan catabolizing enzyme. BMC Biochem. 2, 5 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• van Wissen, M., Snoek, M., Smids, B., Jansen, H. M. & Lutter, R. IFN-γ amplifies IL-6 and IL-8 responses by airway epithelial-like cells via indoleamine 2,3-dioxygenase. J. Immunol. 169, 7039–7044 (2002).
  Article CAS PubMed Google Scholar
• Li, Y., Tredget, E. E. & Ghahary, A. Cell surface expression of MHC class I antigen is suppressed in indoleamine 2,3-dioxygenase genetically modified keratinocytes: implications in allogeneic skin substitute engraftment. Hum. Immunol. 65, 114–123 (2004).
  Article CAS PubMed Google Scholar
• Waldmann, H. & Cobbold, S. Exploiting tolerance processes in transplantation. Science 305, 209–212 (2004).
  Article CAS PubMed Google Scholar
• Munn, D. H. & Mellor, A. L. Macrophages and the regulation of self-reactive T cells. Curr. Pharm. Des. 9, 257–264 (2003).
  Article CAS PubMed Google Scholar
• Parekh, V. V. et al. B cells activated by lipopolysaccharide, but not by anti-Ig and anti-CD40 antibody, induce anergy in CD8+ T cells: role of TGF-β1. J. Immunol. 170, 5897–5911 (2003).
  Article CAS PubMed Google Scholar
• Fillatreau, S., Sweenie, C. H., McGeachy, M. J., Gray, D. & Anderton, S. M. B cells regulate autoimmunity by provision of IL-10. Nature Immunol. 3, 944–950 (2002).
  Article CAS Google Scholar
• Mahnke, K., Qian, Y., Knop, J. & Enk, A. H. Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells. Blood 101, 4862–4869 (2003).
  Article CAS PubMed Google Scholar
• Bilsborough, J., George, T. C., Norment, A. & Viney, J. L. Mucosal CD8α+ DC, with a plasmacytoid phenotype, induce differentiation and support function of T cells with regulatory properties. Immunology 108, 481–492 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Wakkach, A. et al. Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 18, 605–617 (2003).
  Article CAS PubMed Google Scholar
• Faunce, D. E., Terajewicz, A. & Stein-Streilein, J. Cutting edge: _in vitro_-generated tolerogenic APC induce CD8+ T regulatory cells that can suppress ongoing experimental autoimmune encephalomyelitis. J. Immunol. 172, 1991–1995 (2004).
  Article CAS PubMed Google Scholar
• Gilliet, M. & Liu, Y. J. Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J. Exp. Med. 195, 695–704 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Bluestone, J. A. & Abbas, A. K. Natural versus adaptive regulatory T cells. Nature Rev. Immunol. 3, 253–257 (2003).
  Article CAS Google Scholar
• Khattri, R., Cox, T., Yasayko, S. A. & Ramsdell, F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nature Immunol. 4, 337–342 (2003).
  Article CAS Google Scholar
• Bilsborough, J. & Viney, J. L. Getting to the guts of immune regulation. Immunology 106, 139–143 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Wang, H. Y. et al. Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity 20, 107–118 (2004).
  Article CAS PubMed Google Scholar
• Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J. & Schreiber, R. D. Cancer immunoediting: from immunosurveillance to tumor escape. Nature Immunol. 3, 991–998 (2002).
  Article CAS Google Scholar
• Pardoll, D. Does the immune system see tumors as foreign or self? Annu. Rev. Immunol. 21, 807–839 (2003).
  Article CAS PubMed Google Scholar
• Logan, G. J. et al. HeLa cells cocultured with peripheral blood lymphocytes acquire an immuno-inhibitory phenotype through upregulation of indoleamine 2,3-dioxygenase activity. Immunology 105, 478–487 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Huang, A. Y. et al. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 264, 961–965 (1994).
  Article CAS PubMed Google Scholar
• Spiotto, M. T. et al. Increasing tumor antigen expression overcomes 'ignorance' to solid tumors via crosspresentation by bone marrow-derived stromal cells. Immunity 17, 737–747 (2002).
  Article CAS PubMed Google Scholar
• Lee, J. R. et al. Pattern of recruitment of immunoregulatory antigen-presenting cells in malignant melanoma. Lab. Invest. 83, 1457–1466 (2003).
  Article CAS PubMed Google Scholar
• Hartmann, E. et al. Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer. Cancer Res. 63, 6478–6487 (2003).
  CAS PubMed Google Scholar
• Vermi, W. et al. Recruitment of immature plasmacytoid dendritic cells (plasmacytoid monocytes) and myeloid dendritic cells in primary cutaneous melanomas. J. Pathol. 200, 255–268 (2003).
  Article PubMed Google Scholar
• Zou, W. et al. Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nature Med. 7, 1339–1346 (2001).
  Article CAS PubMed Google Scholar
• Grant, R. S. et al. Induction of indoleamine 2,3-dioxygenase in primary human macrophages by human immunodeficiency virus type 1 is strain dependent. J. Virol. 74, 4110–4115 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Burudi, E. M. et al. Regulation of indoleamine 2,3-dioxygenase expression in simian immunodeficiency virus-infected monkey brains. J. Virol. 76, 12233–12241 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Heyes, M. P. et al. Sources of the neurotoxin quinolinic acid in the brain of HIV-1-infected patients and retrovirus-infected macaques. FASEB J. 12, 881–896 (1998).
  Article CAS PubMed Google Scholar
• Kerr, S. J. et al. Kynurenine pathway inhibition reduces neurotoxicity of HIV-1-infected macrophages. Neurology 49, 1671–1681 (1997).
  Article CAS PubMed Google Scholar
• Fuchs, D. et al. Immune activation and decreased tryptophan in patients with HIV-1 infection. J. Interferon Res. 10, 599–603 (1990).
  Article CAS PubMed Google Scholar
• Zangerle, R. et al. Effective antiretroviral therapy reduces degradation of tryptophan in patients with HIV-1 infection. Clin. Immunol. 104, 242–247 (2002).
  Article CAS PubMed Google Scholar
• Garber, K. Make or break for co-stimulatory blockers. Nature Biotechnol. 22, 145–147 (2004).
  Article CAS Google Scholar
• Kremer, J. M. et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4–Ig. N. Engl. J. Med. 349, 1907–1915 (2003).
  Article CAS PubMed Google Scholar
• Waldmann, H. & Cobbold, S. Regulating the immune response to transplants. A role for CD4+ regulatory cells? Immunity 14, 399–406 (2001).
  Article CAS PubMed Google Scholar
• Frolova, L. Y., Grigorieva, A. Y., Sudomoina, M. A. & Kisselev, L. L. The human gene encoding tryptophanyl-tRNA synthetase: interferon-response elements and exon–intron organization. Gene 128, 237–245 (1993).
  Article CAS PubMed Google Scholar
• Fleckner, J., Martensen, P. M., Tolstrup, A. B., Kjeldgaard, N. O. & Justesen, J. Differential regulation of the human, interferon inducible tryptophanyl-tRNA synthetase by various cytokines in cell lines. Cytokine 7, 70–77 (1995).
  Article CAS PubMed Google Scholar
• Tatsumi, K. et al. Induction of tryptophan 2,3-dioxygenase in the mouse endometrium during implantation. Biochem. Biophys. Res. Commun. 274, 166–170 (2000).
  Article CAS PubMed Google Scholar
• Suzuki, S. et al. Expression of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase in early concepti. Biochem. J. 355, 425–429 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Werner-Felmayer, G. et al. Characteristics of interferon induced tryptophan metabolism in human cells in vitro. Biochim. Biophys. Acta 1012, 140–147 (1989).
  Article CAS PubMed Google Scholar
• Ottaviani, E. & Franceschi, C. The invertebrate phagocytic immunocyte:clues to a common evolution of immune and neuroendocrine systems. Immunol. Today 18, 169–174 (1997).
  Article CAS PubMed Google Scholar
• Guilbert, L., Robertson, S. A. & Wegmann, T. G. The trophoblast as an integral component of a macrophage-cytokine network. Immunol. Cell Biol. 71, 49–57 (1993).
  Article CAS PubMed Google Scholar
• Guleria, I. & Pollard, J. W. The trophoblast is a component of the innate immune system during pregnancy. Nature Med. 6, 589–593 (2000).
  Article CAS PubMed Google Scholar
• Grolleau, A. et al. Global and specific translational control by rapamycin in T cells uncovered by microarrays and proteomics. J. Biol. Chem. 277, 22175–22184 (2002).
  Article CAS PubMed Google Scholar
• Harding, H. P. et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol. Cell 11, 619–633 (2003).
  Article CAS PubMed Google Scholar
• Calkhoven, C. F., Muller, C. & Leutz, A. Translational control of gene expression and disease. Trends Mol. Med. 8, 577–583 (2002).
  Article CAS PubMed Google Scholar
• Garcia-Sanz, J. A., Mikulits, W., Livingstone, A., Lefkovits, I. & Mullner, E. W. Translational control: a general mechanism for gene regulation during T cell activation. FASEB J. 12, 299–306 (1998).
  Article CAS PubMed Google Scholar
• Chiarugi, A., Rovida, E., Dello Sbarba, P. & Moroni, F. Tryptophan availability selectively limits NO-synthase induction in macrophages. J. Leukoc. Biol. 73, 172–177 (2003).
  Article CAS PubMed Google Scholar
• Mahnke, K., Knop, J. & Enk, A. H. Induction of tolerogenic DCs: 'you are what you eat'. Trends Immunol. 24, 646–651 (2003).
  Article CAS PubMed Google Scholar
• Ridge, J. P., Di Rosa, F. & Matzinger, P. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 393, 474–478 (1998).
  Article CAS PubMed Google Scholar
• Alpan, O., Bachelder, E., Isil, E., Arnheiter, H. & Matzinger, P. 'Educated' dendritic cells act as messengers from memory to naive T helper cells. Nature Immunol. 5, 615–622 (2004).
  Article CAS Google Scholar
• Thomas, S. R. & Stocker, R. Antioxidant activities and redox regulation of interferon-γ-induced tryptophan metabolism in human monocytes and macrophages. Adv. Exp. Med. Biol. 467, 541–552 (1999).
  Article CAS PubMed Google Scholar
• Mellor, A. L. & Munn, D. H. Tryptophan catabolism prevents maternal T cells from activating lethal anti-fetal immune responses. J. Reprod. Immunol. 52, 5–13 (2001).
  Article CAS PubMed Google Scholar
• Miki, T. et al. Blockade of tryptophan catabolism prevents spontaneous tolerogenicity of liver allografts. Transplant. Proc. 33, 129–130 (2001).
  Article CAS PubMed Google Scholar