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High-level IL-12 production by human dendritic cells requires two signals

Lookup NU author(s): Professor Catharien Hilkens

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Abstract

IL-12 is a key cytokine in the development of Th1 responses. IL-12 production by antigen-presenting cells (APC) can be induced by the interaction between CD40 on the APC and CD40 ligand (CD40L) expressed on T cells after activation. Our previous study indicated that in dendritic cells (DC), the only APC that can activate naive T(h) cells efficiently, the mere CD40 engagement is insufficient to induce IL-12 production. The aim of the present study was to dissect the conditions for efficient IL-12 production by DC further. Using populations of naive and memory Th cells, recombinant CD40L, neutralizing and blocking antibodies, and by determining IFN-gamma production and CD40L expression levels, we here show that T cell-induced IL-12 production by DC results from the action of two signals, mediated by CD40L and IFN-gamma, and that the inability of naive T(h) cells to induce IL-12 production resides in their inability to produce IFN-(gamma). Other factors than CD40L and IFN-gamma can provide the required signals for IL-12 production by DC, as either factor could be replaced by lipopolysaccharide (LPS). The two-signal requirement proved unique for the production of IL-12, since either CD40 engagement or LPS was sufficient for the efficient production of tumor necrosis factor-alpha, IL-8 and the p40 subunit of IL-12, and may be considered as a safety mechanism for optimal control of potentially harmful T(h)1 responses.

Publication metadata

Author(s): Snijders A, Kalinski P, Hilkens CM, Kapsenberg ML

Publication type: Article

Publication status: Published

Journal: International Immunology

Year: 1998

Volume: 10

Issue: 11

Pages: 1593-1598

Print publication date: 01/11/1998

ISSN (print): 0953-8178

ISSN (electronic): 1460-2377

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/intimm/10.11.1593

DOI: 10.1093/intimm/10.11.1593

Notes: 0953-8178 Journal Article

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