title: Identification of IDO-positive and IDO-negative human dendritic cells after activation by various proinflammatory stimuli.
abstract: Dendritic cells (DCs) can induce tolerance or immunity. We identified and characterized an IDO-expressing and an IDO-negative human DC population after stimulation by various proinflammatory stimuli. IDO expression was strongly dependent on the maturation status of the cells (CD83-positive cells only). The two DC subpopulations remained IDO positive and IDO negative, respectively, over a time period of at least 48 h. IDO enzyme activity of human DCs was highest during stimulation by strongly maturation-inducing TLR ligands such as highly purified LPS (TLR4 ligand) or polyriboinosinic-polyribocytidilic acid (TLR3 ligand); factors of the adaptive immune system such as IFN-γ, a mixture of cytokines, and IFN-α had lesser stimulatory capacity for IDO induction and activity. After stimulation with CD40L, IDO-positive DCs expressed significantly increased levels of B7 family molecules such as CD40, CD80, CD86, ICOS ligand, as well as PD-L1 (B7-H1) and PD-L2 (B7-DC) compared with the IDO-negative DC subset. At the same time, the inhibitory receptors Ig-like transcripts 3 and 4 were significantly downregulated on IDO-positive cells. Functionally, IDO-positive DCs produced significantly more IL-1β and IL-15 and less IL-10 and IL-6 than the IDO-negative subset after CD40L stimulation. These results show that IDO expression is associated with a distinctive phenotype and functional capacity in mature DCs. It seems likely that the IDO-positive DC subset possesses a regulatory function and might skew a T cell response toward tolerance.
authors.affiliation: Department of Dermatology and Allergy, Friedrich-Wilhelms-University of Bonn, 53105 Bonn, Germany. d.bubnoff@uni-bonn.de
authors.forename: Dagmar
authors.initials: D
authors.lastname: Von Bubnoff
authors.forename: Marina
authors.initials: M
authors.lastname: Scheler
authors.forename: Helene
authors.initials: H
authors.lastname: Wilms
authors.forename: Rolf
authors.initials: R
authors.lastname: Fimmers
authors.forename: Thomas
authors.initials: T
authors.lastname: Bieber
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000201:enzymology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000032:analysis*; D007249:Inflammation / Q000139:chemically induced*; D007378:Interleukins / Q000096:biosynthesis; D008024:Ligands; D010641:Phenotype; D051193:Toll-Like Receptors / Q000819:agonists
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007378:Interleukins; D008024:Ligands; D051193:Toll-Like Receptors