IL-18 induces the differentiation of Th1 or Th2 cells depending upon cytokine milieu and genetic background

Xu, D., Trajkovic, V., Hunter, D., Leung, B. P., Schulz, K., Gracie, J. A., McInnes, I. B. and Liew, F. Y. (2000) IL-18 induces the differentiation of Th1 or Th2 cells depending upon cytokine milieu and genetic background. European Journal of Immunology, 30(11), pp. 3147-3156. (doi:10.1002/1521-4141(200011)30:11<3147::AID-IMMU3147>3.0.CO;2-J) (PMID:11093129)

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Abstract

The functional division of CD4+ T cells into Th1 and Th2 subsets is generally accepted but the mechanisms leading to their preferential induction remain elusive. Cytokines are considered the main determining factors in the initial differentiation of precursor T cells into these distinct subsets. Thus, IL-12 drives Th1 cells whereas IL-4 drives Th2 cells. Recently IL-18, originally designated as IFN-γ-inducing factor, has been reported to synergize with IL-12 in the induction of Th1 cells. We report here that IL-18 can also induce T cells to differentiate into Th2 cells, in the presence of TCR activation, either alone or together with IL-4. This effect of IL-18 is mediated primarily on CD4+ T cells compared with CD8+ T cells and is inhibited in the presence of IL-12. IL-18, however, has no effect on functionally committed Th2 cells. Moreover, the effect of IL-18 on Th2 cell development is differentially manifest in different mouse strains, suggesting profound underlying genetic influences. BALB/c mice infected with Leishmania major and treated with recombinant IL-18 developed exacerbated disease and enhanced Th2 response compared with untreated controls. These data therefore provide a novel mechanism for Th2 cell development. Thus, IL-18, a cytokine constitutively expressed by cells of the innate response, is capable of inducing Th2 cell differentiation in the absence of IL-4.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Professor Foo and McInnes, Professor Iain and Xu, Dr Damo and Gracie, Professor J Alastair and Leung, Dr Bernard
Authors: Xu, D., Trajkovic, V., Hunter, D., Leung, B. P., Schulz, K., Gracie, J. A., McInnes, I. B., and Liew, F. Y.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:European Journal of Immunology
Publisher:Wiley-VCH Verlag
ISSN:0014-2980
ISSN (Online):1521-4141

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