Differential Capacities of CD4+, CD8+, and CD4−CD8− T Cell Subsets to Express IL-18 Receptor and Produce IFN-γ in Response to IL-18

Abstract IL-12 and IL-18 have the capacity to stimulate IFN-γ production by T cells. Using a T cell clone, we reported that IL-18 responsiveness is generated only after exposure to IL-12. Here, we investigated the induction of IL-18 responsiveness in resting CD8+, CD4+, and CD4−CD8− T cells. Resting T cells respond to neither IL-12 nor IL-18. After stimulation with anti-CD3 plus anti-CD28 mAbs, CD8+, CD4+, and CD4−CD8− T cells expressed IL-12R, but not IL-18R, and produced IFN-γ in response to IL-12. Cultures of T cells with anti-CD3/anti-CD28 in the presence of rIL-12 induced IL-18R expression and IL-18-stimulated IFN-γ production, which reached higher levels than that induced by IL-12 stimulation. However, there was a substantial difference in the expression of IL-18R and IL-18-stimulated IFN-γ production among T cell subsets. CD4+ cells expressed marginal levels of IL-18R and produced small amounts of IFN-γ, whereas CD8+ cells expressed higher levels of IL-18R and produced more IFN-γ than CD4+ cells. Moreover, CD4−CD8− cells expressed levels of IL-18R comparable to those for CD8+ cells but produced IFN-γ one order higher than did CD8+ cells. These results indicate that the induction of IL-18R and IL-18 responsiveness by IL-12 represents a mechanism underlying enhanced IFN-γ production by resting T cells, but the operation of this mechanism differs depending on the T cell subset stimulated.