Natural killer cells from mice deficient in protein kinase C-theta have reduced production of interferon-gamma after stimulation with interleukin-12 (89.32)

Abstract

Abstract NK cells play a key role in innate immune responses. PKC𝛉 is important for T cell activation, but is also expressed in NK cells. NK cells from PKC𝛉 −/− and WT mice were enriched from splenocyte cultures by incubation with IL-15 for one week and then treated for 24 hours with IL-12 or IL-18 to induce IFNγ production. Cytotoxicity of NK cells from PKC𝛉 −/− and WT mice was activated in vivo with poly I:C or in vitro with cytokines, and target cell specific killing measured by 51chromium release assay. NK cell-enriched splenocytes from PKC𝛉 −/− animals produced significantly less IFNγ in response to IL-12, but not in response to IL-18. In contrast, NK cell mediated cytotoxicity was unaffected by the absence of PKC𝛉. T cells, which can also make IFNγ, were not a source of IFNγ in these experiments, nor did they affect the ability of NK cells to produce it. No differences in spleen NK cell numbers or viability were detected. NK cells from PKC𝛉 −/− mice also exhibited normal expression of IL-12Rβ1, and STAT4 proteins and normal IL-12-induced phosporylation of STAT4. Phosphorylation of T538 within the catalytic domain of PKC𝛉 was detectable in NK cells from WT mice, but was not enhanced by IL-12. IFNγ mRNA increased to a similar extent in NK cells from WT and PKC𝛉 −/− mice in response to IL-12. IFNγ mRNA stability was unaffected by the absence of PKC𝛉. These findings indicate a role for PKC𝛉 in the post-transcriptional regulation of IL-12-induced IFNγ.