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Interleukin-12 can directly induce T-helper 1 responses in interferon-gamma (IFN-gamma) receptor-deficient mice, but requires IFN-gamma signalling to downregulate T-helper 2 responses

Mountford, A.P., Coulson, P.S., Cheever, A.W., Sher, A., Wilson, R.A. and Wynn, T.A. (1999) Interleukin-12 can directly induce T-helper 1 responses in interferon-gamma (IFN-gamma) receptor-deficient mice, but requires IFN-gamma signalling to downregulate T-helper 2 responses. Immunology, 97 (4). pp. 588-594. ISSN 0019-2805

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Abstract

An in vivo model of pulmonary granuloma formation around embolized schistosome eggs was investigated as an environment in which to analyse a role for interleukin-12 (IL-12) in the differentiation of T-helper 1 (Th1) and Th2 subsets. Specifically, mice deficient for the interferon-γ receptor (IFN-γR−/–) were used to determine the role for IL-12 in the absence of IFN-γ-mediated signalling. We show that recombinant IL-12 administered to IFN-γR−/– mice caused the up-regulation of mRNA for IFN-γ in lung tissue, and the secretion of abundant IFN-γ by in vitro-cultured lymph node cells in response to egg antigens. This indicates that IL-12 can act independently of IFN-γ to induce the development of Th1 cells. Administration of rIL-12 to wild-type mice markedly reduced the secretion of Th2-associated cytokines, IL-4 and IL-5. However, these cytokines were not dramatically reduced in IFN-γR−/– mice treated with IL-12. We conclude that inhibition of these cytokines by IL-12 is primarily dependent upon effective IFN-γ signalling, although abrogation of T-cell derived IL-10 appeared to be dependent upon IL-12. We also show that increases in mRNA for the β2 subunit of the IL-12 receptor and the p40 subunit of IL-12 after rIL-12 treatment were lower in IFN-γR−/– mice, compared to wild-type mice, indicating that their expression was primarily dependent upon IFN-γ with only a minor role for IL-12.

Item Type: Article
Copyright, Publisher and Additional Information: Open access copy available from the journal web site.
Institution: The University of York
Academic Units: The University of York > Biology (York)
Depositing User: Open Access From Journal
Date Deposited: 22 Dec 2008 14:38
Last Modified: 22 Dec 2008 14:38
Published Version: http://dx.doi.org/10.1046/j.1365-2567.1999.00832.x
Status: Published
Publisher: Wiley-Blackwell
Refereed: Yes
Identification Number: 10.1046/j.1365-2567.1999.00832.x
URI: http://eprints.whiterose.ac.uk/id/eprint/5114

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