International Immunology Advance Access originally published online on November 22, 2005
International Immunology 2005 17(12):1561-1572; doi:10.1093/intimm/dxh335
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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
1 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
2 Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA
Correspondence to: M. Sykes; E-mail: megan.sykes{at}tbrc.mgh.harvard.edu
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-
. 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.
Keywords: dendritic cells, human, prostaglandin E2, T helper 1, T helper 2
Transmitting editor: R. Steinman
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