title: Maturation of human monocyte-derived dendritic cells (MoDCs) in the presence of prostaglandin E2 optimizes CD4 and CD8 T cell-mediated responses to protein antigens: role of PGE2 in chemokine and cytokine expression by MoDCs.
abstract: Prostaglandin E2 (PGE2) acts in synergy with other inflammatory stimuli such as tumor necrosis factor (TNF) to induce the maturation of migratory-type monocyte-derived dendritic cells (MoDCs). However, PGE2 has been reported to inhibit IL-12p70 production by MoDCs and to promote the generation of Th2 T cell responses. We demonstrate here that the addition of PGE2 to TNF for the maturation of MoDCs enhanced CD4 and CD8 T cell proliferative responses to neoantigen and recall antigen, and enhanced Th1-type responses. The increased stimulatory capacity of MoDCs matured with PGE2 was associated with a fully mature, migratory-type MoDC phenotype and more rapid down-regulation of the expression of inflammatory chemokines, with up-regulated expression of the constitutive chemokines TARC and MDC. In addition, although MoDCs matured with TNF and PGE2 selectively produced the inhibitory IL-12p40 subunit at steady state, they were able to produce the bioactive IL-12p70 heterodimer after stimulation with CD40 ligand and/or IFN-gamma. Despite increased IL-6 mRNA expression, MoDCs matured with PGE2 did not overcome the suppressive effects of CD4+ CD25+ T cells in allogeneic mixed lymphocyte reactions. In conclusion, MoDCs matured in the presence of PGE2 display characteristics of more efficient antigen-presenting cells that might be optimal for use in cancer vaccine-based clinical trials.
authors.affiliation: Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, MGH-East, Building 149-5102, 13th Street, Boston 02129, USA.
authors.forename: Marie T
authors.initials: MT
authors.lastname: Rubio
authors.forename: Terry K
authors.initials: TK
authors.lastname: Means
authors.forename: Ronjon
authors.initials: R
authors.lastname: Chakraverty
authors.forename: Juanita
authors.initials: J
authors.lastname: Shaffer
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fudaba
authors.forename: Meredith
authors.initials: M
authors.lastname: Chittenden
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D000941:Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D015232:Dinoprostone / Q000276:immunology / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology
chemical_list: D000941:Antigens; D019496:Cancer Vaccines; D018925:Chemokines; D015232:Dinoprostone