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Gene Review

TNFRSF4  -  tumor necrosis factor receptor superfamily...

Homo sapiens

Synonyms: ACT35, ACT35 antigen, CD134, IMD16, OX40, ...
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Disease relevance of TNFRSF4

  • Soluble OX40 is detectable in serum of subpopulations of healthy donors and patients with autoimmune disease and cancer [1].
  • A marked increase in the percentage of CD134/ CD137+ T cells at disease onset may indicate the need for more aggressive therapy in Graves' disease and for a greater duration than the standard 3-year period [2].
  • After infection with LCMV and influenza virus, OX40-/- mice retain primary and memory cytotoxic T cell responses with normal expansion and decline of specific CTL [3].
  • The HTLV-I tax protein transcriptionally modulates OX40 antigen expression [4].
  • We found that the degree of infiltration by CD25(+) and intratumoral OX40(+) lymphocytes showed a tendency to decrease in thicker melanomas [5].

High impact information on TNFRSF4


Chemical compound and disease context of TNFRSF4

  • These results suggest that immunostaining for OX40/CD134 may be helpful in subclassification of peripheral T-cell lymphomas and that the patterns of TNF receptor family expression in these tumors may parallel those seen within nonneoplastic helper T-cell subsets [9].
  • Four patients with rhinitis and two patients with ACD were available for studying the immunophenotype and the TCR-Vbeta repertoire of bacampicillin induced lymphoblasts as well as the cytokine profiles and expression of the activation markers CD23 and CD134 in primary PBMC cultures [10].

Biological context of TNFRSF4


Anatomical context of TNFRSF4


Associations of TNFRSF4 with chemical compounds

  • CD134 (OX40) is a member of the tumor necrosis factor (TNF) receptor superfamily expressed on activated T cells [11].
  • In the present study, we compared the potency of pimecrolimus and cyclosporin A (CyA) to inhibit cytokine synthesis of alloantigen-primed T cells and the expression of CD134 (OX40), an inducible co-receptor molecule thought to be critical for the survival and expansion of inflammation-mediating T cells [13].
  • The expression of TNFRSF4, one of the genes in this family, was found to be 48 times higher in allergen-challenged cells than in diluent-challenged cells [16].
  • Human peripheral blood lymphocytes sensitised to PPD respond to in vitro stimulation with increased expression of CD69 and CD134 activation antigens and production of Th-1 type cytokines [17].

Regulatory relationships of TNFRSF4

  • Reverse transcriptase-PCR analysis showed that expression of RANTES mRNA was induced after incubation with soluble OX40 and this induction was inhibited by anti-gp34 mAb [18].
  • HUVECs expressing high levels of gp34 were stimulated with recombinant soluble OX40 or mock control and subjected to analysis using cDNA expression arrays [18].

Other interactions of TNFRSF4


Analytical, diagnostic and therapeutic context of TNFRSF4

  • CONCLUSIONS: These results show that CD134-CD134L interaction plays an important role in the co-stimulatory cascade and that blockade of this molecular interaction may be of therapeutic value in helping to prevent allograft rejection [12].
  • With this ELISA, the existence of naturally occurring soluble forms of OX40 (sOX40) could be demonstrated for the first time [1].
  • Identification of a soluble OX40 isoform: development of a specific and quantitative immunoassay [1].
  • In the present study, we identified the rat ligand for OX40 (OX40L) by molecular cloning [21].
  • The heterodimer of OX40 and 4-1BB was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under nonreduced conditions and was associated with the tumor receptor-associated factor (TRAF) family proteins in a unique manner [22].


  1. Identification of a soluble OX40 isoform: development of a specific and quantitative immunoassay. Taylor, L., Schwarz, H. J. Immunol. Methods (2001) [Pubmed]
  2. Analysis of costimulatory molecules OX40/4-1BB (CD134/CD137) detection on chosen mononuclear cells in children and adolescents with Graves' disease during methimazole therapy. Bossowski, A., Stasiak-Barmuta, A., Urban, M., Bossowska, A. J. Pediatr. Endocrinol. Metab. (2005) [Pubmed]
  3. OX40-deficient mice are defective in Th cell proliferation but are competent in generating B cell and CTL Responses after virus infection. Kopf, M., Ruedl, C., Schmitz, N., Gallimore, A., Lefrang, K., Ecabert, B., Odermatt, B., Bachmann, M.F. Immunity (1999) [Pubmed]
  4. The HTLV-I tax protein transcriptionally modulates OX40 antigen expression. Pankow, R., Dürkop, H., Latza, U., Krause, H., Kunzendorf, U., Pohl, T., Bulfone-Paus, S. J. Immunol. (2000) [Pubmed]
  5. T-cell activation marker expression on tumor-infiltrating lymphocytes as prognostic factor in cutaneous malignant melanoma. Ladányi, A., Somlai, B., Gilde, K., Fejös, Z., Gaudi, I., Tímár, J. Clin. Cancer Res. (2004) [Pubmed]
  6. Human T cell leukemia virus type I (HTLV-I) and human diseases. Uchiyama, T. Annu. Rev. Immunol. (1997) [Pubmed]
  7. Signaling through OX40 (CD134) breaks peripheral T-cell tolerance. Bansal-Pakala, P., Jember, A.G., Croft, M. Nat. Med. (2001) [Pubmed]
  8. Selective depletion of myelin-reactive T cells with the anti-OX-40 antibody ameliorates autoimmune encephalomyelitis. Weinberg, A.D., Bourdette, D.N., Sullivan, T.J., Lemon, M., Wallin, J.J., Maziarz, R., Davey, M., Palida, F., Godfrey, W., Engleman, E., Fulton, R.J., Offner, H., Vandenbark, A.A. Nat. Med. (1996) [Pubmed]
  9. The T-cell activation markers CD30 and OX40/CD134 are expressed in nonoverlapping subsets of peripheral T-cell lymphoma. Jones, D., Fletcher, C.D., Pulford, K., Shahsafaei, A., Dorfman, D.M. Blood (1999) [Pubmed]
  10. Characterization of primary recall in vitro lymphocyte responses to bacampicillin in allergic subjects. Cederbrant, K., Marcusson-Stâhl, M., Hultman, P. Clin. Exp. Allergy (2000) [Pubmed]
  11. Functional expression of CD134 by neutrophils. Baumann, R., Yousefi, S., Simon, D., Russmann, S., Mueller, C., Simon, H.U. Eur. J. Immunol. (2004) [Pubmed]
  12. OX40 (CD134) blockade inhibits the co-stimulatory cascade and promotes heart allograft survival. Curry, A.J., Chikwe, J., Smith, X.G., Cai, M., Schwarz, H., Bradley, J.A., Bolton, E.M. Transplantation (2004) [Pubmed]
  13. Pimecrolimus inhibits up-regulation of OX40 and synthesis of inflammatory cytokines upon secondary T cell activation by allogeneic dendritic cells. Kalthoff, F.S., Chung, J., Stuetz, A. Clin. Exp. Immunol. (2002) [Pubmed]
  14. Molecular transfer of CD40 and OX40 ligands to leukemic human B cells induces expansion of autologous tumor-reactive cytotoxic T lymphocytes. Biagi, E., Dotti, G., Yvon, E., Lee, E., Pule, M., Vigouroux, S., Gottschalk, S., Popat, U., Rousseau, R., Brenner, M. Blood (2005) [Pubmed]
  15. Expression of gp34 (OX40 ligand) and OX40 on human T cell clones. Takasawa, N., Ishii, N., Higashimura, N., Murata, K., Tanaka, Y., Nakamura, M., Sasaki, T., Sugamura, K. Jpn. J. Cancer Res. (2001) [Pubmed]
  16. A network-based analysis of allergen-challenged CD4+ T cells from patients with allergic rhinitis. Benson, M., Carlsson, L., Guillot, G., Jernås, M., Langston, M.A., Rudemo, M., Andersson, B. Genes Immun. (2006) [Pubmed]
  17. Human peripheral blood lymphocytes sensitised to PPD respond to in vitro stimulation with increased expression of CD69 and CD134 activation antigens and production of Th-1 type cytokines. Skoberne, M., Malovrh, T., Skralovnik-Stern, A., Kotnik, V. Pflugers Arch. (2000) [Pubmed]
  18. Signaling of gp34 (OX40 ligand) induces vascular endothelial cells to produce a CC chemokine RANTES/CCL5. Kotani, A., Hori, T., Matsumura, Y., Uchiyama, T. Immunol. Lett. (2002) [Pubmed]
  19. Activation of OX40 signal transduction pathways leads to tumor necrosis factor receptor-associated factor (TRAF) 2- and TRAF5-mediated NF-kappaB activation. Kawamata, S., Hori, T., Imura, A., Takaori-Kondo, A., Uchiyama, T. J. Biol. Chem. (1998) [Pubmed]
  20. OX40 costimulation enhances interleukin-4 (IL-4) expression at priming and promotes the differentiation of naive human CD4(+) T cells into high IL-4-producing effectors. Ohshima, Y., Yang, L.P., Uchiyama, T., Tanaka, Y., Baum, P., Sergerie, M., Hermann, P., Delespesse, G. Blood (1998) [Pubmed]
  21. Identification of rat OX40 ligand by molecular cloning. Akiba, H., Atsuta, M., Yagita, H., Okumura, K. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  22. The expression and the regulatory role of OX40 and 4-1BB heterodimer in activated human T cells. Ma, B.Y., Mikolajczak, S.A., Danesh, A., Hosiawa, K.A., Cameron, C.M., Takaori-Kondo, A., Uchiyama, T., Kelvin, D.J., Ochi, A. Blood (2005) [Pubmed]
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