title: IDO expression by human B lymphocytes in response to T lymphocyte stimuli and TLR engagement is biologically inactive.
abstract: The immune system must be under tight control to avoid undesired responses. The enzyme indoleamine 2,3-dioxygenase (IDO) can exert necessary regulating effects by catabolizing tryptophan, leading to the suppression of immune responses in different settings, such as pregnancy and tumor growth. IDO's immuno-suppressive actions are mediated by tryptophan starvation and the accumulation of toxic tryptophan metabolites, resulting in T cell anergy, inhibition of clonal expansion or apoptosis. IDO activity in human macrophages and dendritic cells has been observed after interaction with T lymphocytes, and is triggered by interferon-gamma (IFN-γ) as well as CD40-ligand (CD40L). However, it is unclear whether IDO activity is present in B lymphocytes, which have been identified as having suppressive properties involved in anti-tumor immunity inhibition. In this study, we investigated whether IDO expression is induced in human B cells after exposure to T lymphocyte stimuli and TLR ligands. We report IDO1 and IDO2 mRNA up-regulation by exogenous stimulation with CD40L and IFN-γ. IDO is also upregulated by imiquimod, a TLR 7/8 agonist. In addition, IDO protein is detected after treatment with these exogenous factors or with supernatant from activated CD4(+) T cells. We, however, report weak or absent enzymatic activity from these IDO-expressing cells, as assessed by tryptophan consumption. We conclude that IDO may not be a counter-regulatory mechanism utilized by B lymphocytes to down-regulate immune responses, although its expression is inducible.
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal - Hôpital Notre-Dame, Department of Medicine, Université de Montréal, Institut du cancer de Montréal, Montréal, Québec, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Godin-Ethier
authors.forename: Laïla-Aïcha
authors.initials: LA
authors.lastname: Hanafi
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Duvignaud
authors.forename: Denis
authors.initials: D
authors.lastname: Leclerc
authors.forename: Réjean
authors.initials: R
authors.lastname: Lapointe
mesh_terms: D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D015153:Blotting, Western; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008856:Microscopy, Fluorescence; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D051193:Toll-Like Receptors