IL-18 was originally cloned as a IFN-γ inducing factor in primed T cells. In synergy with IL-12, IL-18 has been shown to induce strikingly high levels of IFN-γ production by T cells and to enhance Th1 development. Also this cytokine exerts induction of Th2 development through IL-4 induction.

Resting CD4⁺ T cells were sorted by negative selection and activated by anti-CD3 plus anti-CD28 Ab. Expression of IL-12 binding sites, IL-18 binding sites, IL-18Rα, and GATA-3 mRNA were analysed by FACS and RT-PCR, respectively.

Resting CD4⁺ T cells expressed IL-18Rα chain but not IL-18 binding sites, suggesting a lack of IL-18Rβ expression. IL-18Rα was maintained on the Th1 and Th2 committed cells. IL-18 binding sites were induced on the Th1 but not Th2 cells. Exposure of these cells to IL-18 led to up-regulation of GATA-3 mRNA expression only in Th2 committed cells. To elucidate the relationship between IL-18Rα expression and GATA-3 induction by IL-18, Th1 and Th2 committed cells were further cultured in medium with or without IL-12 for 2 days. IL-12 binding sites were maintained on the Th1 and Th2 cells regardless of IL-12 treatment, but IL-18Rα expression was rapidly down-regulated on the IL-12-untreated Th2 cells which did not induce GATA-3 mRNA expression followed by IL-18 stimulation.

IL-12 supports expression of IL-18Rα and GATA-3 mRNA expression was induced by IL-18 through IL-18Rα without expression of IL-18 binding site in Th2 cells.