Journal Article

Poly(I:C) used for human dendritic cell maturation preserves their ability to secondarily secrete bioactive IL‐12

Redouane Rouas, Philippe Lewalle, Frank El Ouriaghli, Berengere Nowak, Hughes Duvillier and Philippe Martiat

in International Immunology

Published on behalf of Japanese Society for Immunology

Volume 16, issue 5, pages 767-773
Published in print May 2004 | ISSN: 0953-8178
Published online May 2004 | e-ISSN: 1460-2377 | DOI: https://dx.doi.org/10.1093/intimm/dxh077

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Dendritic cells (DC) are professional antigen‐presenting cells that play a central role in the control of immunity. Mature DC are characterized by high expression levels of MHC and co‐stimulatory molecules, and by the secretion of IL‐12, a key cytokine for the priming of cytotoxic T lymphocytes. Here, we have compared different maturation stimuli to reproducibly generate stable mature DC secreting high amounts of bioactive IL‐12p70. We have compared soluble human trimeric CD40 ligand (sCD40L) combined with IFN‐γ, poly(I:C), a cocktail of cytokines (IL‐1β, IL‐6 and tumor necrosis factor‐α) with prostaglandin E2 and lipopolysaccharide. A major concern, however, is whether DC, that have already produced high amounts of IL‐12p70 during the maturation step, are still capable of secreting IL‐12p70 after in vivo administration at the time of interaction with the targeted T cells. To mimic that situation, mature DC generated by those methods were compared for their ability to secrete IL‐12p70 in the absence of IFN‐γ, using sCD40L. We observed a second consistent secretion of bioactive IL‐12p70 upon subsequent sCD40L stimulation only when poly(I:C) was used as the maturating agent. Our data suggest that, for clinical use, poly(I:C) may be one of the most appropriate agents to generate stable mature DC. These mature DC might generate in vivo effective immune responses after injection, because they retain the ability to secrete bioactive IL‐12 after CD40 ligation.

Keywords: CD40 ligand, IL‐12, immunotherapy, mature dendritic cell

Journal Article.  4574 words.  Illustrated.

Subjects: Immunology ; Biological Sciences