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International Immunology Advance Access originally published online on December 15, 2008
International Immunology 2009 21(2):145-153; doi:10.1093/intimm/dxn132
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

IL-23 modulates CD56+/CD3– NK Cell and CD56+/CD3+ NK-like T Cell function differentially from IL-12

Diederik van de Wetering, Roelof A. de Paus, Jaap T. van Dissel and Esther van de Vosse

Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands

Correspondence to: E. van de Vosse; E-mail: e.van_de_vosse{at}lumc.nl

NK and NK-like T cells play an essential role in linking innate and adaptive immunity through their ability to secrete IFN-{gamma}. The exact trigger initiating production of IFN-{gamma} is uncertain. Antigen-presenting cell (APC)-derived IL-12 is thought to be the classical IFN-{gamma}-inducing cytokine but requires an additional stimulus such as IFN-{gamma} itself. IL-23 and IL-18 are among the first cytokines secreted by APC in response to binding of pathogen-associated molecular patterns such as LPS. Thus, early APC-derived IL-23 may be an initial trigger of IFN-{gamma} production in NK and NK-like T cells. Herein, we characterized the effect of IL-23 on IFN-{gamma} secretion by NK and NK-like T cells. Our findings show that IL-23 and IL-18 synergistically elicit IFN-{gamma} production in NK-like T cells but not in NK cells. In contrast, IL-12 together with IL-18-induced secretion of IFN-{gamma} in both populations. The observed synergy between IL-23 and IL-18 in NK-like T cells coincided with IL-23-mediated up-regulation of IL-18R{alpha}. Furthermore, IL-23 up-regulated CD56 expression in NK-like T cells and, together with IL-18, induced proliferation of NK and NK-like T cells. We postulate a role for APC-derived IL-23 in the activation of NK and NK-like T cells early in infection and in shaping Th1 differentiation, via induction of IFN-{gamma}, which provides the additional stimulus needed for APC to subsequently produce IL-12.

Keywords: human, IL-18, IL-23, innate immunity

Transmitting editor: G. Trinchieri

Received 17 June 2008, accepted 18 November 2008.


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