title: The ratio between dendritic cells and T cells determines whether prostaglandin E2 has a stimulatory or inhibitory effect.
abstract: 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.
authors: Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany. shima@uk-koeln.de
authors: Alexander
authors: A
authors: Shimabukuro-Vornhagen
authors: Tanja M
authors: TM
authors: Liebig
authors: Thomas
authors: T
authors: Koslowsky
authors: Sebastian
authors: S
authors: Theurich
authors: Michael S
authors: MS
authors: von Bergwelt-Baildon
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000378:metabolism; D018655:Lymphocyte Count; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D015232:Dinoprostone