Article
Indoleamine 2,3-dioxygenase tissue distribution and cellular localization in mice: implications for its biological functions.
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, MS-1018, room KLSIC-4061, 2146 W. 39 Ave., Kansas City, KS 66160, USA.
Journal of Histochemistry and Cytochemistry (impact factor:
2.72).
10/2009;
58(1):17-28.
DOI:10.1369/jhc.2009.953604
Source: PubMed
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Article: CDllc+ cells modulate pulmonary immune responses by production of indoleamine 2,3-dioxygenase.
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ABSTRACT: Interactions between antigen-presenting cells and T cells can result in T cell activation or suppression. With the use of RNA analysis, high-performance liquid chromatography, mixed leukocyte reactions (MLRs), and animal models, the current study reports that lung interstitial antigen-presenting cells (iAPCs, CDllc+) suppress T cell responses in vitro and in vivo by production of indoleamine 2,3-dioxygenase (IDO), an enzyme that catabolizes tryptophan to its byproduct, kynurenine. IDO mRNA expression was unique to lung iAPCs, as cells similarly isolated from the liver and spleen did not express IDO constitutively, or in response to interferon-gamma. Lung iAPCs suppressed proliferation of allogeneic T cells, correlating with increased kynurenine levels; and blockade of IDO activity with 1-methyl-DL-tryptohan (1-MT) or addition of exogenous tryptophan recovered T cell proliferation in MLRs. In contrast, liver and splenic iAPCs were potent stimulators of T cells in MLRs, and IDO inhibition had no effect on T cell responses. In vivo studies showed that systemic blockade of IDO resulted in spontaneous proliferation in lung T cells and pulmonary inflammation. Finally, overexpressing IDO in lung transplants abrogated acute allograft rejection, a T cell-mediated disease. Collectively these data show that lung iAPCs contribute to local regulation of cellular immune responses by production of IDO.American Journal of Respiratory Cell and Molecular Biology 04/2004; 30(3):311-8. · 5.13 Impact Factor -
Article: Studies on indoleamine 2,3-dioxygenase. I. Superoxide anion as substrate.
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ABSTRACT: Indoleamine 2,3-dioxygenase purified to apparent homogeneity from rabbit intestine was inhibited by scavengers for superoxide anion such as superoxide dismutase and 1,2-dihydroxybenzene-3,5-disulfonic acid (Tiron). On the other hand, beta-carotene and 1,4-diazobicyclo-(2,2,2)-octane, scavengers for singlet oxygen, did not affect the enzyme activity significantly. The degree of inhibition of the dioxygenase by superoxide dismutase preparations from bovine erythrocytes, green peas, spinach leaves, and Escherichia coli paralleled that observed with these dismutase preparations on the aerobic reduction of cytochrome c by xanthine oxidase and its substrate. The pH profiles of the inhibition by dismutase of the dioxygenase and cytochrome c reduction were also similar and the maximal inhibition was observed around pH 10 in both cases. The degree of inhibition was not affected by the concentration of substrate but was a function of the concentration of dismutase. It was inversely related to the concentrations of the dioxygenase and its cofactors, ascorbic acid and methylene blue, both of which were required for maximum activity. Ascorbic acid could be replaced either by xanthine oxidase and its substrate, or by tetrabutylammonium superoxide prepared by electrolytic reduction of molecular oxygen, or by potassium superoxide. When limited amounts of superoxide anion were added to the reaction mixture containing a substrate amount of the dioxygenase, the ratio of the amount of superoxide anion added to that of the product formed was approximately unity both under aerobic and anaerobic conditions. Taken together, these findings indicate that superoxide anion, rather than molecular oxygen, is utilized as substrate by indoleamine 2,3-dioxygenase.Journal of Biological Chemistry 09/1975; 250(15):5960-6. · 4.77 Impact Factor -
Article: Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion.
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ABSTRACT: In mice, immunoregulatory APCs express the dendritic cell (DC) marker CD11c, and one or more distinctive markers (CD8alpha, B220, DX5). In this study, we show that expression of the tryptophan-degrading enzyme indoleamine 2,3 dioxygenase (IDO) is selectively induced in specific splenic DC subsets when mice were exposed to the synthetic immunomodulatory reagent CTLA4-Ig. CTLA4-Ig did not induce IDO expression in macrophages or lymphoid cells. Induction of IDO completely blocked clonal expansion of T cells from TCR transgenic mice following adoptive transfer, whereas CTLA4-Ig treatment did not block T cell clonal expansion in IDO-deficient recipients. Thus, IDO expression is an inducible feature of specific subsets of DCs, and provides a potential mechanistic explanation for their T cell regulatory properties.The Journal of Immunology 09/2003; 171(4):1652-5. · 5.79 Impact Factor
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Keywords
antigen-presenting cells
bioactive tryptophan catabolites
capsular cells
cellular localization
cellular localization characteristics
constitutive IDO expression
different situations
enclosed microenvironment
epididymal duct lumen
highest levels
IDO expression
indoleamine 2,3-dioxygenase
initial segment
luminal compartment
morphological features
stained cells
T-cell-mediated immune responses
various mouse tissues
viral infection
wide tissue distribution