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

IL-12 and IL-18 have the capacity to stimulate IFN-gamma 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 i nduction of IL-18 responsiveness in resting CD8(+), CD4(+), and CD4(-) CD8(-) T cells, Resting T cells respond to neither IL-12 nor IL-18, Af ter stimulation with anti-CD3 plus anti-CD28 mAbs, CD8(+), CD4(+), and CD4(-)CD8(-) T cells expressed IL-12R, but not IL-18R, and produced I FN-gamma 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-sti mulated IFN-gamma production, which reached higher levels than that in duced by IL-12 stimulation, However, there was a substantial differenc e in the expression of IL-18R and IL-18-stimulated IFN-gamma productio n among T cell subsets, CD4(+) cells expressed marginal levels of IL-1 8R and produced small amounts of IFN-gamma, whereas CD8(+) cells expre ssed higher levels of IL-18R and produced more IFN-gamma than CD4(+) c ells, Moreover, CD4(-)CD8(-) cells expressed levels of IL-18R comparab le to those for CD8(+) cells but produced IFN-gamma one order higher t han did CD8(+) cells, These results indicate that the induction of IL- 18R and IL-18 responsiveness by IL-12 represents a mechanism underlyin g enhanced IFN-gamma production by resting T cells, but the operation of this mechanism differs depending on the T cell subset stimulated.