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© The Rockefeller University Press, 0022-1007/1998/10/1485/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 8, October 19, 1998 1485-1492

Articles

Selective Expression and Functions of Interleukin 18 Receptor on T Helper (Th) Type 1 but not Th2 Cells

Damo Xu*, Woon Ling Chan{ddagger}, Bernard P. Leung*, David Hunter*, Kerstin Schulz*, Robert W. Carter{ddagger}, Iain B. McInnes*, John H. Robinson§, and Foo Y. Liew*

From the * Department of Immunology, University of Glasgow, Glasgow G11 6NT, United Kingdom; the {ddagger} Department of Virology, St. Bartholomew and Royal London School of Medicine, Queen Mary and Westfield College, University of London, London EC1A 7BE, United Kingdom; and the § Department of Immunology, University of Newcastle, Newcastle Upon Tyne NE2 4HH, United Kingdom

Interleukin (IL)-18 induces interferon (IFN)-{gamma} 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-{alpha}β transgenic mice (D011.10). Anti–IL-18R antibody inhibited IL-18– induced IFN-{gamma} 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-{gamma} 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.

Key Words: T helper type 1 cells • T helper type 2 cells • interleukin 18 receptor • inflammation • septic shock

Address correspondence to Foo Y. Liew, Department of Immunology, University of Glasgow, Glasgow G11 6NT, Scotland, UK. Phone: 44-141-211-2695; Fax: 44-141-337-3217; E-mail: f.y.liew{at}clinmed.gla.ac.uk or Woon Ling Chan, Department of Virology, St. Bartholomew and Royal London School of Medicine, Queen Mary and Westfield College, University of London, London EC1A 7BE, UK. Phone: 44-171-601-7355; Fax: 44-171-726-4248; E-mail: w.l.chan{at}mds.qmw.ac.uk

Abbreviations used: DLN, draining lymph node(s); HPRT, hypoxanthine phosphoribosyltransferase; IL-1Rrp, IL-1 receptor–related protein; RT, reverse transcription.


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