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

J Exp Med. 1998 Oct 19;188(8):1485-92. doi: 10.1084/jem.188.8.1485.

Abstract

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-12Rbeta2 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-alphabeta 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Inflammation / prevention & control
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / pharmacology
  • Interleukin-18 / pharmacology
  • Interleukin-18 Receptor alpha Subunit
  • Lipopolysaccharides / toxicity
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Receptors, Interleukin / physiology*
  • Receptors, Interleukin-18
  • Shock, Septic / prevention & control
  • Th1 Cells / physiology*
  • Th2 Cells / physiology*

Substances

  • Il18r1 protein, mouse
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Lipopolysaccharides
  • Receptors, Interleukin
  • Receptors, Interleukin-18
  • Interleukin-12
  • Interferon-gamma