Cytokine expression by murine DX5+ cells in response to IL-12, IL-18, or the combination of IL-12 and IL-18

In this study we analyzed the response of DX5(+) NK and NK T cells to in vitro stimulation with IL-12 or IL-18. Production of IFN-gamma in response to either IL-12 or IL-18 was dependent upon costimulation with either IL-2 or IL-15. DX5(+) splenocytes showed a rapid (6 h) and sustained (6-72 h) accumulation of IFN-gamma transcripts followed by a delayed (12-24 h) up-regulation of IL-10 or IL-13 expression in response to IL-2 + IL-12 or IL-2 + IL-18, respectively. Incubation of DX5(+) splenocytes with the combination of IL-2 + IL-12 + IL-18 resulted in up-regulation of IFN-gamma and IL-13 transcripts but down-regulation of IL-10 expression. Furthermore, two distinct populations of cells producing differing amounts of IFN-gamma were observed by intracellular staining after stimulation with IL-2 + IL-12 + IL-18. Last, we demonstrate that DX5(+) cells respond to IL-18 independently of IL-12, as cells from both wild-type and IL-12R beta 2KO mice produce IFN-gamma and IL-13 in response to IL-2 + IL-18. (C) 2001 Academic Press.