Targeted disruption of Traf5 gene causes defects in CD40- and CD27-mediated lymphocyte activation.
TRAF5 [tumor necrosis factor (TNF) receptor-associated factor 5] is implicated in NF-kappaB and c-Jun NH(2)-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-kappaB or c-Jun NH(2)-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.
Nakano
H
H
Department of Immunology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. hnakano@med.juntendo.ac.jp
Sakon
S
S
Koseki
H
H
Takemori
T
T
Tada
K
K
Matsumoto
M
M
Munechika
E
E
Sakai
T
T
Shirasawa
T
T
Akiba
H
H
Kobata
T
T
Santee
S M
SM
Ware
C F
CF
Rennert
P D
PD
Taniguchi
M
M
Yagita
H
H
Okumura
K
K
D000818:Animals; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D048015:TNF Receptor-Associated Factor 5; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011506:Proteins; D048015:TNF Receptor-Associated Factor 5; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D023201:CD40 Ligand; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases