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Indoleamine 2,3-dioxygenase expression and functional activity in dendritic cells exposed to cholera toxin

Slavica, L;Nurkkala-Karlsson, M;Karlson, T;Ingelsten, M;Nystrm, J;Eriksson, K;

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.