The ratio between dendritic cells and T cells determines whether prostaglandin E2 has a stimulatory or inhibitory effect

Prostaglandin E2 has been shown to enhance the maturation, migration, and antigen-presenting capacity of DCs. It is therefore included in many maturation cocktails for the generation of monocyte-derived DCs. Paradoxically, PGE2 is also an important tumor-derived immunosuppressive factor and has inhibitory effects on DC differentiation and function. To further investigate these seemingly contradictory results we studied whether the DC:T cell ratio has an impact on the outcome of the interaction between PGE2-treated DCs and T cells. Surprisingly, at high DC:T cell ratios T cell proliferation was inhibited while at low ratios PGE2-treated DCs displayed enhanced T cell-stimulatory properties. The inhibitory function of PGE2-treated DCs depended primarily on the PGE2-induced induction of indoleamine 2,3-dioxygenase competence. In summary, we show that PGE2-treated DCs can have either an immunogenic or tolerogenic function depending on the DC:T cell ratio. This finding could explain the conflicting results regarding the influence of PGE2 on DC function.

► Depending on the DC:T cell ratio PGE2-treated DCs have opposite effects on T cells. ► At high ratios DCs are immunostimmulatory while at low ratios they are tolerogenic. ► The tolerogenic effect of PGE2-treated DCs depends on the induction of IDO. ► Inhibition of IDO inhibits the tolerogenic effects of PGE2 at high DC:T cell ratios.