Targeted disruption of Traf5 gene causes defects in CD40- and CD27- mediated lymphocyte activation

H. Nakano, S. Sakon, H. Koseki, T. Takemori, K. Tada, M. Matsumoto, E. Munechika, T. Sakai, T. Shirasawa, H. Akiba, T. Kobata, S. M. Santee, C. F. Ware, P. D. Rennert, M. Taniguchi, H. Yagita, K. Okumura

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Abstract

TRAF5 [tumor necrosis factor (TNF) receptor-associated factor 5] is implicated in NF-κB and c-Jun NH2-terminal kinase/stress-activated protein kinase activation by members of the TNF receptor superfamily, including CD27, CD30, CD40, and lymphotoxin-β receptor. To investigate the functional role of TRAF5 in vivo, we generated TRAF5-deficient mice by gene targeting. Activation of either NF-κB or c-Jun NH2-terminal kinase/stress-activated protein kinase by tumor necrosis factor, CD27, and CD40 was not abrogated in traf5(-/-) mice. However, traf5(-/-) B cells showed defects in proliferation and up-regulation of various surface molecules, including CD23, CD54, CD80, CD86, and Fas in response to CD40 stimulation. Moreover, in vitro Ig production of traf5(-/-) B cells stimulated with anti-CD40 plus IL-4 was reduced substantially. CD27-mediated costimulatory signal also was impaired in traf5(-/-) T cells. Collectively, these results demonstrate that TRAF5 is involved in CD40- and CD27-mediated signalling.

Original languageEnglish
Pages (from-to)9803-9808
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number17
DOIs
Publication statusPublished - Aug 17 1999

All Science Journal Classification (ASJC) codes

  • General

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    Nakano, H., Sakon, S., Koseki, H., Takemori, T., Tada, K., Matsumoto, M., Munechika, E., Sakai, T., Shirasawa, T., Akiba, H., Kobata, T., Santee, S. M., Ware, C. F., Rennert, P. D., Taniguchi, M., Yagita, H., & Okumura, K. (1999). Targeted disruption of Traf5 gene causes defects in CD40- and CD27- mediated lymphocyte activation. Proceedings of the National Academy of Sciences of the United States of America, 96(17), 9803-9808. https://doi.org/10.1073/pnas.96.17.9803