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-γ production and enhances NK 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 of125I-labeled hIL-18 to IL-18R-expressing L428 cells. This mAb also neutralized hIL-18-induced T helper 1 type cytokine (IFN-γ and GM-CSF) production by Con A-stimulated PBMC. PBMC 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 CD8+T cells as well as on CD56+NK 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 NK cells.