International Immunology, Vol. 12, No. 2, 151-160,
February 2000
© 2000 Japanese Society for Immunology
IL-12 synergizes with IL-18 or IL-1ß for IFN-
production from human T cells
1 Third Department of Internal Medicine,
2 Department of Immunology and Medical Zoology, and
3 Laboratory of Host Defenses, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya 663-8501, Japan
4 Fujisaki Institute, Hayashibara Biochemical Laboratories, Okayama 702-8006, Japan
5 CREST of Japan Science and Technology Corp., Tokyo 101-0062, Japan
Correspondence to: K. Nakanishi, Department of Immunology and Medical Zoology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
IL-18 is a proinflammatory cytokine that plays an important role in NK cell activation and Th1 response. IL-18 has a structural homology to IL-1, particularly IL-1ß. IL-18R, composed of IL-1R-related protein (IL-18R
) and IL-1R accessory protein-like (IL-18Rß), belongs to the IL-1R family. Furthermore, IL-18R at least partly shares the signal transducing system with IL-1R. Thus, the IL-18–IL-18R system has a striking similarity to the IL-1–IL-1R system. For this reason, we regarded it important to investigate whether, like IL-18, IL-1ß synergizes with IL-12 in inducing IFN-
production from human T cells and plays an important role in the Th1 response. Here we show that IL-12 and IL-1ß synergistically induce T cells to proliferate and produce IFN- without their TCR engagement. IL-12 stimulation induced an increase in the proportion of T cells positive for IL-18R. Then, IL-12-stimulated T cells responded to IL-18 or IL-1ß by their proliferation and IFN- production, although levels of IL-1ß-induced responses were lower. CD4+CD45RA+ T cells, although they constitutively expressed IL-18Rß mRNA, did not express IL-18R mRNA. Phytohemagglutinin (PHA) stimulation alone induced IL-18R mRNA without affecting the expression of IL-18Rß mRNA. Th1-inducing conditions (PHA, IL-12 and anti-IL-4) further increased this expression. We also show that Th1 cells but not Th2 cells have increased expression of IL-18R and IL-1R, and produce IFN- in response to IL-18 and/or IL-1ß.
Keywords: IL-12, IL-18, IL-1ß, IFN-, human Th1
Transmitting editor: T. Watanabe
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