DIFFERENTIAL CAPACITIES OF CD4+, CD8+, AND CD4-CD8- T CELL SUBSETS TO EXPRESS IL-18 RECEPTOR AND PRODUCE IFN-GAMMA IN RESPONSE TO IL-18

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.