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Publication Detail
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.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Rubio MT, Means TK, Chakraverty R, Shaffer J, Fudaba Y, Chittenden M, Luster AD, Sykes M
  • Publication date:
  • Pagination:
    1561, 1572
  • Journal:
    Int Immunol
  • Volume:
  • Issue:
  • Status:
  • Country:
  • Print ISSN:
  • PII:
  • Language:
  • Keywords:
    Antigen Presentation, Antigens, CD8-Positive T-Lymphocytes, Cancer Vaccines, Cell Differentiation, Cells, Cultured, Chemokines, Dendritic Cells, Dinoprostone, Gene Expression Regulation, Humans, Monocytes, T-Lymphocytes, Regulatory, Th1 Cells
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.
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