Natural killer cells from protein kinase C θ-/- mice stimulated with interleukin-12 are deficient in production of interferon-γ

Protein kinase C theta (PKC theta) is expressed in NK cells, but its functional role has not been defined. Here, we demonstrate involvement of PKC theta in IL-12-induced NK cell IFN-gamma production. NK cells from PKC theta(-/-) mice produced less IFN-beta in response to IL-12 than those from wild-type (WT) mice. IL-12-induced NK cell cytotoxicity was unaffected, and NK cells from PKC theta(-/-) mice did not display reduced IFN-gamma production in response to IL-18, indicating a specific role for PKC theta in IL-12-induced IFN-gamma production. Under the conditions tested, T cells did not produce IFN-gamma in response to IL-12 or affect the ability of NK cells to produce the cytokine. PKC theta deficiency did not affect NK cell numbers, granularity, viability, or cytotoxic activity in response to polyinosinic: polycytydylic acid. NK cells from PKC theta(-/-) mice exhibited normal expression of IL-12R beta 1 and STAT4 proteins and normal induction of STAT4 phosphorylation in response to IL-12. Phosphorylation of threonine 538 within the catalytic domain of PKC theta was detectable in NK cells from WT mice but was not enhanced by IL-12. Transcription of IFN-gamma increased similarly in NK cells from WT and PKC theta(-/-) mice in response to IL-12, and there was no difference in IFN-gamma mRNA stability. Taken together, these findings indicate a role for PKC theta in the post-transcriptional regulation of IL-12-induced IFN-gamma production.