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Increased production of pro-inflammatory cytokines and enhanced T cell responses after activation of human dendritic cells with IL-1 and CD40 ligand.

Abstract : BACKGROUND: Various microbial, inflammatory and immune signals regulate the activation of dendritic cells (DC), determining their ability to interact with na? T cells and to produce cytokines that direct T cell development. In particular, CD40L and IL-1 cooperatively activate DC to secrete high levels of IL-12. The immuno-stimulatory capacity of such DC is otherwise not well-defined prompting further characterization of the effects of IL-1 and family members on DC activation in comparison with other pro-inflammatory stimuli. RESULTS: Human DC co-activated in vitro by CD40L and IL-1beta expressed numerous cytokine genes including IL-12beta, IL-23 p19, IL-1beta, IL-1alpha, IL-1Ra, IL-10, IL-6, IL-18 and IFN-gamma. These DC produced high levels of IL-12 protein and appeared capable of producing IFN-gamma. Potent CD4+ and CD8+ T cell-stimulatory properties were acquired by DC under conditions that also induced IL-12. Notably, these DC induced rapid differentiation of fluMP-specific CD8+ T cells. Molecules related to IL-1beta, like IL-1alpha, co-induced IL-12 secretion whereas IL-18 did not. Conversely, the inhibitor IL-1Ra, produced endogenously by DC curtailed IL-12 production in response to CD40L. CONCLUSIONS: IL-1 and IL-1Ra play a biologically-relevant role in the positive and negative regulation of DC activation. In conjunction with CD40L, IL-1 sends a powerful activation signal to DC that could be distinguished from other modes of activation. This signal enables the production of pro-inflammatory cytokines by DC, and enhances the differentiation of na? T cells into effectors of type-1 cellular immune responses.
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https://www.hal.inserm.fr/inserm-00123511
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Submitted on : Wednesday, January 10, 2007 - 10:14:19 AM
Last modification on : Wednesday, August 7, 2019 - 2:56:02 PM
Long-term archiving on: : Friday, September 21, 2012 - 10:01:07 AM

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  • HAL Id : inserm-00123511, version 1
  • PUBMED : 12385649

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Amy Wesa, Anne Galy. Increased production of pro-inflammatory cytokines and enhanced T cell responses after activation of human dendritic cells with IL-1 and CD40 ligand.. BMC Immunology, BioMed Central, 2002, 3, pp.14. ⟨inserm-00123511⟩

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