Prostaglandin E2 is a key factor for monocyte-derived dendritic cell maturation:: enhanced T cell stimulatory capacity despite IDO

The exclusive ability of dendritic cells (DCs) to stimulate primary and secondary immune responses favors the use of antigen-loaded human monocyte-derived DCs (MoDCs) in vaccinations against tumors. Previous studies demonstrated that PGE(2) is fundamental during MoDC maturation to facilitate migration toward lymph node-derived chemokines. A recent study challenged the use of PGE2, as PGE2 induced IDO in mature MoDCs. In MoDCs compatible for clinical use, we now demonstrate that PGE2 is responsible for IDO induction if matured by soluble CD40 ligand, LPS, or cytokines. In contrast, IDO expression in MoDCs matured by TLR3 triggering occurs independently of PGE2. It is surprising that despite active IDO protein, MoDCs matured with PGE2 display a greater potential to stimulate naive CD4(+) and CD8(+) T cell proliferation, which is not increased further by IDO inhibition. Moreover, we found elevated levels of tryptophanyl-tRNA-synthetase (TTS) in T cells cultured with PGE(2)-matured MoDCs. Our data demonstrate that PGE2 induces IDO in MoDCs but that T cell-stimulating capacities of PGE2-matured MoDCs overcome IDO activity, probably through TTS induction. As PGE2 is critical for DC migration and enhances the capability of MoDCs to induce T cell proliferation, we highly recommend supplementing DC maturation stimuli with PGE2 for use in clinical trials.