Indoleamine 2,3-dioxygenase Expression and Functional Activity in Dendritic Cells Exposed to Cholera Toxin

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.