TNF receptor-associated factor 5 limits the induction of Th2 immune responses

J Immunol. 2004 Apr 1;172(7):4292-7. doi: 10.4049/jimmunol.172.7.4292.


The TNF receptor-associated factor (TRAF) family of molecules acts as adapter proteins for signaling pathways initiated by several members of the TNF receptor (TNFR) superfamily. TRAF5(-/-) animals are viable and have normal development of the immune system despite interacting with several TNFR family members. A clear role for TRAF5 has yet to emerge. OX40 (CD134) interacts with TRAF5, suggesting that this pathway could be involved in regulating T cell differentiation into Th1 or Th2 cells. In tissue culture, OX40 stimulation of TRAF5(-/-) T cells resulted in a pronounced Th2 phenotype with elevated levels of IL-4 and IL-5. Similarly, in vivo immunization with protein in adjuvant in the presence of an agonist anti-OX40 Ab resulted in enhanced Th2 development in TRAF5(-/-) mice. Additionally, lung inflammation induced by T cells, which is critically controlled by OX40, was more pronounced in TRAF5(-/-) mice, characterized by higher levels of Th2 cytokines. These results suggest that TRAF5 can limit the induction of Th2 responses, and that TRAF5 can play a role in modulating responses driven by OX40 costimulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Inflammation / genetics
  • Inflammation / immunology
  • Injections, Intraperitoneal
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Protein Biosynthesis
  • Proteins / genetics
  • Proteins / physiology*
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor / immunology
  • Signal Transduction / immunology*
  • TNF Receptor-Associated Factor 5
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism*
  • Tumor Necrosis Factor-alpha / physiology*


  • Cytokines
  • Proteins
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • TNF Receptor-Associated Factor 5
  • Tnfrsf4 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Ovalbumin