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

Prostaglandin E-2 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, PGE(2) 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 PGE(2)-treated DCs and T cells. Surprisingly, at high DC:T cell ratios T cell proliferation was inhibited while at low ratios PGE(2)-treated DCs displayed enhanced T cell-stimulatory properties. The inhibitory function of PGE(2)-treated DCs depended primarily on the PGE(2)-induced induction of indoleamine 2,3-dioxygenase competence. In summary, we show that PGE(2)-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 PGE(2) on DC function. (c) 2013 Elsevier Inc. All rights reserved.