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Gene Review

TNFSF4  -  tumor necrosis factor (ligand) superfamily...

Homo sapiens

Synonyms: CD134L, CD252, GP34, Glycoprotein Gp34, OX-40L, ...
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Disease relevance of TNFSF4


High impact information on TNFSF4


Biological context of TNFSF4


Anatomical context of TNFSF4

  • Identification of a human OX-40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor [11].
  • Using a soluble form of the receptor, the extracellular region fused with human immunoglobulin Fc, we expression cloned the human OX-40 ligand cDNA from a library derived from an activated B lymphoblastoid cell line MSAB [11].
  • We describe gp34 as a new member of the TNF family, and find that the recombinant ligand expressed in COS cells costimulates phorbol myristate acetate, phytohemagglutinin, and anti-CD3-induced CD4+ T cell proliferation [11].
  • We expressed both CD40L and OX40L on B-CLL cells by exploiting the phenomenon of molecular transfer from fibroblasts overexpressing these ligands [12].
  • Expression and function of OX40 ligand on human dendritic cells [13].

Associations of TNFSF4 with chemical compounds


Regulatory relationships of TNFSF4

  • TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand [7].
  • HUVECs expressing high levels of gp34 were stimulated with recombinant soluble OX40 or mock control and subjected to analysis using cDNA expression arrays [17].
  • OX40L strongly inhibited the generation of IL-10-producing Tr1 cells induced by two physiologic stimuli, the inducible costimulatory ligand and immature dendritic cells [14].
  • Furthermore, treatment of pDCs with NO decreased production of IL-6 and TNF-alpha and up-regulated OX40 ligand expression [18].

Other interactions of TNFSF4

  • CD40L or OX40L alone was insufficient to expand tumor-reactive T cells [12].
  • In addition, these are the first studies to demonstrate that the combined use of a vector driving the expression of OX40L with three other costimulatory molecules (B7-1, ICAM-1, and LFA-3) both enhances initial activation and then further potentiates sustained activation of nai;ve and effector T cells [19].
  • Here we show that OX40L is expressed on dendritic cells (DC), the most efficient APC to prime naive T cells [13].
  • Ligation of OX40L resulted in a rapid translocation of protein kinase C beta2 to the cell membrane [20].
  • However, during maturation in response to Sendai virus over the longer 72-h period, the expression level of OX40L was up-regulated, whereas the residual IFN-alpha-producing ability was down-regulated, and consequently, the PDCs with prolonged Sendai virus stimulation induced Th2 responses to some extent [21].

Analytical, diagnostic and therapeutic context of TNFSF4


  1. Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility. Wang, X., Ria, M., Kelmenson, P.M., Eriksson, P., Higgins, D.C., Samnegård, A., Petros, C., Rollins, J., Bennet, A.M., Wiman, B., de Faire, U., Wennberg, C., Olsson, P.G., Ishii, N., Sugamura, K., Hamsten, A., Forsman-Semb, K., Lagercrantz, J., Paigen, B. Nat. Genet. (2005) [Pubmed]
  2. 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]
  3. Molecular cloning and characterization of a novel glycoprotein, gp34, that is specifically induced by the human T-cell leukemia virus type I transactivator p40tax. Miura, S., Ohtani, K., Numata, N., Niki, M., Ohbo, K., Ina, Y., Gojobori, T., Tanaka, Y., Tozawa, H., Nakamura, M. Mol. Cell. Biol. (1991) [Pubmed]
  4. OX40 expressed on fresh leukemic cells from adult T-cell leukemia patients mediates cell adhesion to vascular endothelial cells: implication for the possible involvement of OX40 in leukemic cell infiltration. Imura, A., Hori, T., Imada, K., Kawamata, S., Tanaka, Y., Imamura, S., Uchiyama, T. Blood (1997) [Pubmed]
  5. Regulation of T cell activation in vitro and in vivo by targeting the OX40-OX40 ligand interaction: amelioration of ongoing inflammatory bowel disease with an OX40-IgG fusion protein, but not with an OX40 ligand-IgG fusion protein. Higgins, L.M., McDonald, S.A., Whittle, N., Crockett, N., Shields, J.G., MacDonald, T.T. J. Immunol. (1999) [Pubmed]
  6. Dysregulation of CD30+ T cells by leukemia impairs isotype switching in normal B cells. Cerutti, A., Kim, E.C., Shah, S., Schattner, E.J., Zan, H., Schaffer, A., Casali, P. Nat. Immunol. (2001) [Pubmed]
  7. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. Ito, T., Wang, Y.H., Duramad, O., Hori, T., Delespesse, G.J., Watanabe, N., Qin, F.X., Yao, Z., Cao, W., Liu, Y.J. J. Exp. Med. (2005) [Pubmed]
  8. Identification of rat OX40 ligand by molecular cloning. Akiba, H., Atsuta, M., Yagita, H., Okumura, K. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  9. Enhancing the immunostimulatory function of dendritic cells by transfection with mRNA encoding OX40 ligand. Dannull, J., Nair, S., Su, Z., Boczkowski, D., DeBeck, C., Yang, B., Gilboa, E., Vieweg, J. Blood (2005) [Pubmed]
  10. T cell proliferation by direct cross-talk between OX40 ligand on human mast cells and OX40 on human T cells: comparison of gene expression profiles between human tonsillar and lung-cultured mast cells. Kashiwakura, J., Yokoi, H., Saito, H., Okayama, Y. J. Immunol. (2004) [Pubmed]
  11. Identification of a human OX-40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor. Godfrey, W.R., Fagnoni, F.F., Harara, M.A., Buck, D., Engleman, E.G. J. Exp. Med. (1994) [Pubmed]
  12. 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]
  13. Expression and function of OX40 ligand on human dendritic cells. Ohshima, Y., Tanaka, Y., Tozawa, H., Takahashi, Y., Maliszewski, C., Delespesse, G. J. Immunol. (1997) [Pubmed]
  14. OX40 ligand shuts down IL-10-producing regulatory T cells. Ito, T., Wang, Y.H., Duramad, O., Hanabuchi, S., Perng, O.A., Gilliet, M., Qin, F.X., Liu, Y.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  15. CD4 T cell traffic control: in vivo evidence that ligation of OX40 on CD4 T cells by OX40-ligand expressed on dendritic cells leads to the accumulation of CD4 T cells in B follicles. Brocker, T., Gulbranson-Judge, A., Flynn, S., Riedinger, M., Raykundalia, C., Lane, P. Eur. J. Immunol. (1999) [Pubmed]
  16. Ligand-induced association between the T-cell antigen receptor and two glycoproteins. Fraser, J.D., Goldsmith, M.A., Weiss, A. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  17. 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]
  18. Nitric oxide inhibits IFN-alpha production of human plasmacytoid dendritic cells partly via a guanosine 3',5'-cyclic monophosphate-dependent pathway. Morita, R., Uchiyama, T., Hori, T. J. Immunol. (2005) [Pubmed]
  19. A recombinant vector expressing transgenes for four T-cell costimulatory molecules (OX40L, B7-1, ICAM-1, LFA-3) induces sustained CD4+ and CD8+ T-cell activation, protection from apoptosis, and enhanced cytokine production. Grosenbach, D.W., Schlom, J., Gritz, L., Gómez Yafal, A., Hodge, J.W. Cell. Immunol. (2003) [Pubmed]
  20. Detection and characterization of OX40 ligand expression in human airway smooth muscle cells: a possible role in asthma? Burgess, J.K., Carlin, S., Pack, R.A., Arndt, G.M., Au, W.W., Johnson, P.R., Black, J.L., Hunt, N.H. J. Allergy Clin. Immunol. (2004) [Pubmed]
  21. Plasmacytoid dendritic cells regulate Th cell responses through OX40 ligand and type I IFNs. Ito, T., Amakawa, R., Inaba, M., Hori, T., Ota, M., Nakamura, K., Takebayashi, M., Miyaji, M., Yoshimura, T., Inaba, K., Fukuhara, S. J. Immunol. (2004) [Pubmed]
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