International Immunology Advance Access published online on November 22, 2005
International Immunology, doi:10.1093/intimm/dxh335
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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
* To whom correspondence should be addressed. 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-
Received March 23, 2005
Accepted September 15, 2005
Article
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
Marie T. Rubio 1,
Terry K. Means 2,
Ronjon Chakraverty 1,
Juanita Shaffer 1,
Yasuhiro Fudaba 1,
Meredith Chittenden 1,
Andrew D. Luster 2,
and
Megan Sykes 1 *
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
Megan Sykes, E-mail: megan.sykes{at}tbrc.mgh.harvard.edu
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Abstract
. 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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