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Original Article |
Production in CCAAT/Enhancer Binding Protein
deficient Mice
Correspondence to: Shizuo Akira, Dept. of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. Tel:81-6-6879-8302 Fax:81-6-6879-8305 E-mail:sakira{at}biken.osaka-u.ac.jp.
We have investigated in vivo roles of CCAAT/enhancer binding protein
(C/EBP
) by gene targeting. C/EBP
-deficient (C/EBP
2/-) mice showed a high mortality rate within 48 h after birth. To analyze the roles of C/EBP
in lymphoid lineage cells, bone marrow chimeras were established. C/EBP
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/EBP
-/- chimera splenocytes to produce interferon (IFN)-
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
2/- newborn spleen cells. However, they also showed lower cytotoxic activity and IFN-
production when stimulated with IL-12 plus IL-18 than control NK cells, as observed in C/EBP
2/- chimera splenocytes. In conclusion, our study reveals that C/EBP
is a critical transcription factor involved in the functional maturation of NK cells.
Key Words:
gene targeting, natural killer cells, C/EBP
, interleukin 15, interferon
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