Impairment of natural killer cytotoxic activity and interferon γ production in CCAAT/enhancer binding protein γ-deficient mice

We have investigated in vivo roles of CCAAT/enhancer binding protein gamma (C/EBP gamma) by gene targeting. C/EBP gamma-deficient (C/EBP gamma(-/-)) mice showed a high mortality rate within 48 h after birth. To analyze the roles of C/EBP gamma in lymphoid lineage cells, bone marrow chimeras were established. C/EBP gamma(-/-) chimeras showed normal T and B cell development. However, cytolytic functions of their splenic natural killer (NK) cells after stimulation with cytokines such as interleukin (IL)-12, IL-18, and IL-2 were significantly reduced as compared with those of control chimera NK cells. In addition, the ability of C/EBP gamma(-/-) chimera splenocytes to produce interferon (IFN)-gamma in response to IL-12 and/or IL-18 was markedly impaired. NK cells could be generated in vitro with normal surface marker expression in the presence of IL-15 from C/EBP gamma(-/-) newborn spleen cells. However, they also showed lower cytotoxic activity and IFN-gamma production when stimulated with IL-12 plus IL-18 than control NK cells, as observed in C/EBP gamma(-/-) chimera splenocytes. In conclusion, our study reveals that C/EBP gamma is a critical transcription factor involved in the functional maturation of NK cells.