Selective expression and functions of Interleukin 18 receptor on T Helper (Th) type 1 but not Th2 cells

Xu, D., Chan, W. L., Leung, B. P., Hunter, D., Schulz, K., Carter, R. W., McInnes, I. B. , Robinson, J. H. and Liew, F. Y. (1998) Selective expression and functions of Interleukin 18 receptor on T Helper (Th) type 1 but not Th2 cells. Journal of Experimental Medicine, 188(8), pp. 1485-1492. (doi:10.1084/jem.188.8.1485) (PMID:9782125) (PMCID:PMC2213413)

Xu, D., Chan, W. L., Leung, B. P., Hunter, D., Schulz, K., Carter, R. W., McInnes, I. B. , Robinson, J. H. and Liew, F. Y. (1998) Selective expression and functions of Interleukin 18 receptor on T Helper (Th) type 1 but not Th2 cells. Journal of Experimental Medicine, 188(8), pp. 1485-1492. (doi:10.1084/jem.188.8.1485) (PMID:9782125) (PMCID:PMC2213413)

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Abstract

Interleukin (IL)-18 induces interferon (IFN)-γ synthesis and synergizes with IL-12 in T helper type 1 (Th1) but not Th2 cell development. We report here that IL-18 receptor (IL-18R) is selectively expressed on murine Th1 but not Th2 cells. IL-18R mRNA was expressed constitutively and consistently in long-term cultured clones, as well as on newly polarized Th1 but not Th2 cells. IL-18 sustained the expression of IL-12Rβ2 mRNA, indicating that IL-18R transmits signals that maintain Th1 development through the IL-12R complex. In turn, IL-12 upregulated IL-18R mRNA. Antibody against an IL-18R–derived peptide bound Th1 but not Th2 clones. It also labeled polarized Th1 but not Th2 cells derived from naive ovalbumin–T cell antigen receptor-αβ transgenic mice (D011.10). Anti–IL-18R antibody inhibited IL-18– induced IFN-γ production by Th1 clones in vitro. In vivo, anti–IL-18R antibody reduced local inflammation and lipopolysaccharide-induced mortality in mice. This was accompanied by shifting the balance from Th1 to Th2 responses, manifest as decreased IFN-γ and proinflammatory cytokine production and increased IL-4 and IL-5 synthesis. Therefore, these data provide a direct mechanism for the selective effect of IL-18 on Th1 but not Th2 cells. They also show that the synergistic effect of IL-12 and IL-18 on Th1 development may be due to the reciprocal upregulation of their receptors. Furthermore, IL-18R is a cell surface marker distinguishing Th1 from Th2 cells and may be a therapeutic target.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Professor Foo and McInnes, Professor Iain and Xu, Dr Damo and Hunter, Mr David and Leung, Dr Bernard
Authors: Xu, D., Chan, W. L., Leung, B. P., Hunter, D., Schulz, K., Carter, R. W., McInnes, I. B., Robinson, J. H., 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:Journal of Experimental Medicine
Publisher:Rockefeller University Press
ISSN:0022-1007
ISSN (Online):1540-9538

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