Impairment of natural killer cytotoxic activity and interferon gamma production in CCAAT/enhancer binding protein gamma-deficient mice.
We have investigated in vivo roles of CCAAT/enhancer binding protein gamma (C/EBPgamma) by gene targeting. C/EBPgamma-deficient (C/EBPgamma(2/-)) mice showed a high mortality rate within 48 h after birth. To analyze the roles of C/EBPgamma in lymphoid lineage cells, bone marrow chimeras were established. C/EBPgamma(2/-) 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/EBPgamma(-/-) 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/EBPgamma(2/-) 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/EBPgamma(2/-) chimera splenocytes. In conclusion, our study reveals that C/EBPgamma is a critical transcription factor involved in the functional maturation of NK cells.
Pubmed ID: 10587348 RIS Download
Animals | CCAAT-Enhancer-Binding Proteins | Chimera | Cytotoxicity, Immunologic | DNA-Binding Proteins | Flow Cytometry | Interferon-gamma | Interleukin-12 | Interleukin-18 | Interleukin-18 Receptor alpha Subunit | Killer Cells, Natural | Liver | Mice | Mice, Inbred BALB C | Mice, Knockout | Nuclear Proteins | Receptors, Interleukin | Receptors, Interleukin-12 | Receptors, Interleukin-18 | Restriction Mapping | Reverse Transcriptase Polymerase Chain Reaction | Signal Transduction | Spleen | Transcription Factors