title: Dendritic cells matured by a prostaglandin E2-containing cocktail can produce high levels of IL-12p70 and are more mature and Th1-biased than dendritic cells treated with TNF-α or LPS.
abstract: Dendritic cells (DCs) play a crucial role in the initiation of an immune response. As maturation is critical for effective antigen presentation, different methods have been used to generate mature DCs (mDCs) ex vivo. The use of a maturation cocktail (MC) consisting of IL-1β, IL-6, TNF-α, and prostaglandin E2 (PGE2) initially showed promising results, but then was challenged because of low production of IL-12p70 and the potential for induction of Th2-type immune responses. To investigate this contention, we compared two of the most commonly used maturation factors, TNF-α and LPS, with MC. Maturation cocktail was superior to TNF-α and LPS with respect to enhancement of mDC-specific surface marker expression (CD83, CD86, and HLA-DR), induction of T cell proliferation by mDCs, and directional motility of mDCs toward CCL19. These results were supported by increased expression of a significant number of additional maturation-related genes by MC in comparison to TNF-α and LPS. In addition, we did not observe a Th2-biased shift in the gene expression profile of mDCs generated by MC. Conversely, MC induced more Th1-promoting transcriptional changes than LPS or TNF-α, including increased transcript levels of Th1-type cytokines such as IL-15, IL-12β, and EBI3 (IL-27β) and MHC class I molecules, Th1-promoting changes in the transcripts of CXCL16, CCL13, and CCL18, and reduced transcript levels of MHC class II molecules. More interestingly, the Th1-promoting characteristics of MC-mDCs were confirmed by their potential to produce large amounts of IL-12p70 after effective stimulation simulating in vivo events.
authors.affiliation: Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Rd, Saskatoon, SK S7N5E3, Canada.
authors.forename: Abdolamir
authors.initials: A
authors.lastname: Landi
authors.forename: Lorne A
authors.initials: LA
authors.lastname: Babiuk
authors.forename: Sylvia
authors.initials: S
authors.lastname: van Drunen Littel-van den Hurk
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D002478:Cells, Cultured; D046508:Culture Techniques / Q000379:methods*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D015232:Dinoprostone