Constitutive and induced IL-18 receptor expression by various peripheral blood cell subsets as determined by anti-hIL-18R monoclonal antibody

Interleukin-18 (IL-18) was identified as a molecule that induces IFN-gamma production and enhances NH cell cytotoxicity. Characterization of the receptor for human IL-18 (hIL-18R) is important for investigating the physiological role of IL-18 in nature. In the present study, we describe a monoclonal antibody (mAb) against hIL-18R (mAb No. 117-10C). This mAb inhibited the binding of I-125-labeled hIL-18 to IL-18R-expressing L428 cells. This mAb also neutralized hIL-18-induced T helper 1 type cytokine (IFN-gamma and GM-CSF) production by Con A-stimulated PBMC. PEMC were examined for the expression of IL-18R by two-color flow cytometry. Most CD19(+) B cells and a percentage of CD8(+) T cells were found to constitutively express IL-18R. Treatment of PBMC with IL-12 preferentially induced IL-18R expression on CD56(+) NK cells regardless of costimulation with mitogen. IL-18R expression on CD4(+) T cells was induced weakly by IL-12 treatment and moderately by PHA stimulation. However, neither could IL-12 treatment nor PHA stimulation induce IL-18R expression on CD8(+) T cells. Costimulation with both IL-12 and PHA was necessary for optimal IL-18R expression on CDS' T cells as well as on CD56(+) NH cells, CD4(+) T cells, and CD19(+) B cells. These results support the growing number of reports showing that IL-18 has modulatory effects on T, B, and NH cells. (C) 1998 Academic Press.