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.
Bibliography
Xu, D., Chan, W. L., Leung, B. P., Hunter, D., Schulz, K., Carter, R. W., McInnes, I. B., Robinson, J. H., & Liew, F. Y. (1998). Selective Expression and Functions of Interleukin 18 Receptor on T Helper (Th) Type 1 but not Th2 Cells. The Journal of Experimental Medicine, 188(8), 1485â1492.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 12:49 p.m.) |
Deposited | 2 years, 1 month ago (July 25, 2023, 5:44 a.m.) |
Indexed | 3 months, 3 weeks ago (May 16, 2025, 12:05 a.m.) |
Issued | 26 years, 10 months ago (Oct. 19, 1998) |
Published | 26 years, 10 months ago (Oct. 19, 1998) |
Published Online | 26 years, 10 months ago (Oct. 19, 1998) |
Published Print | 26 years, 10 months ago (Oct. 19, 1998) |
@article{Xu_1998, title={Selective Expression and Functions of Interleukin 18 Receptor on T Helper (Th) Type 1 but not Th2 Cells}, volume={188}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.188.8.1485}, DOI={10.1084/jem.188.8.1485}, number={8}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Xu, Damo and Chan, Woon Ling and Leung, Bernard P. and Hunter, David and Schulz, Kerstin and Carter, Robert W. and McInnes, Iain B. and Robinson, John H. and Liew, Foo Y.}, year={1998}, month=oct, pages={1485–1492} }