title: Indoleamine 2,3-dioxygenase expression and functional activity in dendritic cells exposed to cholera toxin.
abstract: Indoleamine 2,3-dioxygenase (IDO), a tryptophan-metabolizing enzyme expressed by dendritic cells (DC), has the potential to inhibit T cell responses and to promote tolerance. In contrast, cholera toxin (CT), the enterotoxin produced by Vibrio cholerae, promotes T cell responses, partly through its ability to induce DC maturation and promote antigen presentation. We hypothesized that the adjuvant activity of CT is associated with a lack of induction of IDO in DC. To test this hypothesis, monocyte-derived DC were pulsed with CT, and the IDO mRNA expression, IDO functional activity and cytokine production were measured as well as the ability of DC to induce T cell responses in vitro. Cholera toxin exposure induced enhanced levels of IDO mRNA in DC but no functional IDO protein activity. Cholera toxin pulsing however primed DC for CD40L-induced IDO protein activity. CD40L stimulation of CT-pulsed DC induced a modest IL-12p40 production, but not IL-12p70 or IL-23 secretion. Furthermore, CT-pulsed DC induced strong allogeneic and autologous T cell responses in vitro, which were not affected by the IDO-specific inhibitor 1-methyl tryptophan. Our results show that CT per se does not induce the expression of functional IDO protein, although it primes DC for CD40L-mediated IDO production and IL-12p40 secretion. Furthermore, CT-treated DC were equally powerful in their T cell stimulatory capacity as cytokine-matured DC.
authors.affiliation: Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden. lucija.slavica@rheuma.gu.se
authors.forename: L
authors.initials: L
authors.lastname: Slavica
authors.forename: M
authors.initials: M
authors.lastname: Nurkkala-Karlsson
authors.forename: T
authors.initials: T
authors.lastname: Karlson
authors.forename: M
authors.initials: M
authors.lastname: Ingelsten
authors.forename: J
authors.initials: J
authors.lastname: Nyström
authors.forename: K
authors.initials: K
authors.lastname: Eriksson
mesh_terms: D023201:CD40 Ligand / Q000276:immunology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000276:immunology*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology*; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000276:immunology; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D014734:Vibrio cholerae / Q000276:immunology*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053762:Interleukin-12 Subunit p40; D023201:CD40 Ligand; D002772:Cholera Toxin