title: Regulation of human auto- and alloreactive T cells by indoleamine 2,3-dioxygenase (IDO)-producing dendritic cells: too much ado about IDO?
abstract: Although dendritic cells (DCs) strongly stimulate the immune response, they can also induce unresponsiveness. Recently, a human monocyte-derived DC subpopulation was described that constitutively expresses indoleamine 2,3-dioxygenase (IDO). These DCs were defined as nonadherent CD123+/CC chemokine receptor 6+ (CCR6+) cells that suppress the allogeneic T-cell response. In the present study, we generated nonadherent, mature DCs from human blood monocytes. As expected, in addition to the classic markers, these cells expressed CD123 and CCR6. Reverse transcription-polymerase chain reaction (RT-PCR), however, did not show IDO gene transcription, nor did we detect enzymatic IDO activity. Treating the cells with interferon-gamma (IFN-gamma) resulted in significant IDO production. Subsequently, we studied the regulatory properties of IDO-producing DCs on autologous and allogeneic T-cell responses. Neither OKT3-stimulated T cells of healthy donors nor myelin basic protein (MBP)-specific T cells of patients with multiple sclerosis (MS) were suppressed by autologous IDO DCs. However, whereas IDO(neg) DCs supported further stimulation of preactivated MBP-specific T cells of an MS patient, IDO(pos) DCs had lost this capacity. The allogeneic T-cell response was only marginally suppressed by IDO DCs. Our findings show that nonadherent CD123+/CCR6+ human DCs do not constitutively express IDO, and, even if they express the enzyme after IFN-gamma treatment, they possess only limited T-cell regulatory function.
authors.affiliation: Institute of Immunology, University of Heidelberg, INF-305, 69120 Heidelberg, Germany. peter.terness@med.uni-heidelberg.de
authors.forename: Peter
authors.initials: P
authors.lastname: Terness
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Chuang
authors.forename: Thomas
authors.initials: T
authors.lastname: Bauer
authors.forename: Lucian
authors.initials: L
authors.lastname: Jiga
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D053650:Interleukin-3 Receptor alpha Subunit; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D009103:Multiple Sclerosis / Q000201:enzymology / Q000276:immunology; D016853:Muromonab-CD3 / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; C106311:CCR6 protein, human; C115022:IL3RA protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053650:Interleukin-3 Receptor alpha Subunit; D007519:Isoantigens; D016853:Muromonab-CD3; D004676:Myelin Basic Protein; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D016185:Receptors, Interleukin-3; D007371:Interferon-gamma