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

被引：162

作者：

Nakano, H

Sakon, S

Koseki, H

Takemori, T

Tada, K

Matsumoto, M

Munechika, E

Sakai, T

Shirasawa, T

Akiba, H

Kobata, T

Santee, SM

Ware, CF

Rennert, PD

Taniguchi, M

Yagita, H

Okumura, K

机构：

[1] Juntendo Univ, Sch Med, Dept Immunol, Bunkyo Ku, Tokyo 1138421, Japan

[2] Japan Sci & Technol Corp, Core Res Evolut Sci & Technol, Chiyoda Ku, Tokyo 1010062, Japan

[3] Chiba Univ, Grad Sch, Dept Mol Embryol, Chuo Ku, Chiba 2600856, Japan

[4] Chiba Univ, Grad Sch, Dept Mol Immunol, Chuo Ku, Chiba 2600856, Japan

[5] Natl Inst Infect Dis, Dept Immunol, Shinjuku Ku, Tokyo 1620052, Japan

[6] Univ Tokushima, Inst Enzyme Res, Div Informat Cytol, Tokushima 7708503, Japan

[7] Tokyo Metropolitan Inst Gerontol, Dept Mol Genet, Itabashi Ku, Tokyo 1730015, Japan

[8] La Jolla Inst Allergy & Immunol, Div Mol Immunol, San Diego, CA 92121 USA

[9] Biogen Inc, Dept Immunol & Inflammat, Cambridge, MA 02142 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1999年 / 96卷 / 17期

关键词：

D O I：

10.1073/pnas.96.17.9803

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

TRAF5 [tumor necrosis factor (TNF) receptor-associated factor 5] is implicated in NF-kappa B and c-Jun NH2-terminal kinase/stress-activated protein kinase activation by members of the TNF receptor superfamily, including CD27, CD30, CD40, and lymphotoxin-beta receptor. To investigate the functional role of TRAF5 in vivo, we generated TRAF5-deficient mice by gene targeting. Activation of either NF-kappa B or c-dun 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 signaling.

引用

页码：9803 / 9808

页数：6

共 34 条

[1] CD27, a member of the tumor necrosis factor receptor superfamily, activates NF-KB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-KB-inducing kinase [J].