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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

Author(s): Wesa Amy | Galy Anne

Journal: BMC Immunology
ISSN 1471-2172

Volume: 3;
Issue: 1;
Start page: 14;
Date: 2002;
Original page

Keywords: IL-1 | CD40L | IL-12 | IL-23 | dendritic cells | human

Abstract Background Various microbial, inflammatory and immune signals regulate the activation of dendritic cells (DC), determining their ability to interact with naïve 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-1β expressed numerous cytokine genes including IL-12β, IL-23 p19, IL-1β, IL-1α, IL-1Ra, IL-10, IL-6, IL-18 and IFN-γ. These DC produced high levels of IL-12 protein and appeared capable of producing IFN-γ. 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-1β, like IL-1α, 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 naïve T cells into effectors of type-1 cellular immune responses.
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