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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

Authors

  • Kaisho T
  • Tsutsui H
  • Tanaka T
  • Tsujimura T
  • Takeda K
  • Kawai T
  • Yoshida N
  • Nakanishi K
  • Akira S

Journal

The Journal of experimental medicine

Publication Data

December 6, 1999

Associated Grants

None

Mesh Terms

  • 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