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-γ 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-γ 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-γ and IL-13 transcripts but down-regulation of IL-10 expression. Furthermore, two distinct populations of cells producing differing amounts of IFN-γ 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-12Rβ2KO mice produce IFN-γ and IL-13 in response to IL-2 + IL-18.