title: Targeted disruption of Traf5 gene causes defects in CD40- and CD27-mediated lymphocyte activation.
abstract: 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.
authors.affiliation: Department of Immunology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. hnakano@med.juntendo.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Nakano
authors.forename: S
authors.initials: S
authors.lastname: Sakon
authors.forename: H
authors.initials: H
authors.lastname: Koseki
authors.forename: T
authors.initials: T
authors.lastname: Takemori
authors.forename: K
authors.initials: K
authors.lastname: Tada
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: E
authors.initials: E
authors.lastname: Munechika
authors.forename: T
authors.initials: T
authors.lastname: Sakai
authors.forename: T
authors.initials: T
authors.lastname: Shirasawa
authors.forename: H
authors.initials: H
authors.lastname: Akiba
authors.forename: T
authors.initials: T
authors.lastname: Kobata
authors.forename: S M
authors.initials: SM
authors.lastname: Santee
authors.forename: C F
authors.initials: CF
authors.lastname: Ware
authors.forename: P D
authors.initials: PD
authors.lastname: Rennert
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: K
authors.initials: K
authors.lastname: Okumura
mesh_terms: 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*
chemical_list: 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