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Gene Review

TNFSF8  -  tumor necrosis factor (ligand) superfamily...

Homo sapiens

Synonyms: CD153, CD30 ligand, CD30-L, CD30L, CD30LG, ...
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Disease relevance of TNFSF8


High impact information on TNFSF8

  • Thus, CD30 triggering by CD30L-expressing cells may plan an important role in the activation of HIV expression from latently infected CD4+ T cells [7].
  • The anti-CD30L antibody also exerted a suppressive effect on spontaneous HIV replication occurring in lymph node cells from an HIV-sero-positive patient, showing CD30L expression by both B and CD8+ T lymphocytes [7].
  • CD30 is a member of the tumor necrosis factor receptor superfamily, preferentially expressed by T cells producing type 2 helper (Th2) cytokines, whose ligand (CD30L) has been identified on B cells, activated macrophages, and a subset of activated T cells [7].
  • Cross-linking of CD30 induces HIV expression in chronically infected T cells [8].
  • Thus, CD30-CD30L interactions mediate the induction of HIV expression by a kappa B-dependent pathway that is independent of TNF [8].

Chemical compound and disease context of TNFSF8


Biological context of TNFSF8

  • Dysregulation of CD30+ T cells by leukemia impairs isotype switching in normal B cells [11].
  • Engagement of CD153 (CD30 ligand) by CD30+ T cells inhibits class switch DNA recombination and antibody production in human IgD+ IgM+ B cells [12].
  • In addition, CD153 engagement inhibits IgG, IgA, and IgE production, and this effect is associated with reduced levels of B lymphocyte maturation protein-1 transcripts, and increased binding of B cell-specific activation protein to the Ig 3' enhancer [12].
  • The binding of CD30 by its ligand provides new opportunities for controlling cell growth and treatment of CD30+ ALCL [2].
  • Observed pleiotropic effects of CD30 signaling are most likely dependent on cell cycle status and signal strength [2].

Anatomical context of TNFSF8

  • In addition, engagement of T cell CD30 by CD30L on neoplastic CLL B cells down-regulates the CD3-induced expression of CD40L [11].
  • These findings provide additional information on the nature and localization of CD30+ thymocytes and show that epithelial cells are the major holder of CD30L in the thymic medulla [13].
  • Moreover, many medullary epithelial cells and Hassal's corpuscles in the same thymus specimens showed unusually high expression of CD30L in comparison with other lymphoid or nonlymphoid tissues [13].
  • The ligand for CD30 (CD30L) is a membrane-associated glycoprotein related to TNF, which is known to be expressed mainly by activated T cells and other leukocytes [13].
  • In the normal thyroid tissue, colloid nodules, and another subset of benign and malignant thyroid nodules, IL-6 expression is under control of signals other than CD30L/CD30 [4].

Associations of TNFSF8 with chemical compounds

  • All 15 follicular cancers (FTC), all 6 anaplastic cancers (ATC) were IL-6/lL-6R negative; 14/15 FTC and 5/6 ATC were CD30L/CD30 negative [4].
  • Understanding the physiological role of CD30 would be an important step forward in transplants because CD30+ T cells can be induced by alloantigens even in the presence of immunosuppressives such as cyclosporine (Csa) and hence can act as regulatory cells in allograft [14].
  • After isopropyl beta-D-thiogalactoside induction, the M(r) 37,000 His(10)-tagged Ang-CD30L was directed into the periplasmic space and functionally purified by a combination of metal ion affinity followed by enterokinase cleavage of the His(10)-Tag and molecular size chromatography [15].
  • Taken together, the results suggest that CD30L induces the tyrosine phosphorylation and activation of the MAPK p42ERKII isoform in HDLM-2 cells [9].
  • We have previously reported that IL-7 signals regulate CD30L expression [16].

Physical interactions of TNFSF8

  • Soluble CD30 binds to CD153 with high affinity and blocks transmembrane signaling by CD30 [17].

Regulatory relationships of TNFSF8


Other interactions of TNFSF8

  • Upon exposure to IL-4, a critical Ig class switch-inducing cytokine, Ag-activated T cells express CD30, the CD153 receptor [12].
  • CD30 ligand (CD30L), but not its cognate receptor CD30, is frequently expressed on acute myeloid leukaemia (AML) blasts [19].
  • Depriving H/RS cells from CD30L and CD40L survival signals by eliminating B cells from HD lesions may be of therapeutic value [20].
  • While CD40 and CD30L surface protein expression on PB monocytes could be enhanced or induced by treatment with gamma-interferon, these cells remained negative for CD30, both at the mRNA and at the protein level [21].
  • Ang-CD30L showed RNase activity in vitro [15].

Analytical, diagnostic and therapeutic context of TNFSF8


  1. ADAM10 Inhibition of Human CD30 Shedding Increases Specificity of Targeted Immunotherapy In vitro. Eichenauer, D.A., Simhadri, V.L., von Strandmann, E.P., Ludwig, A., Matthews, V., Reiners, K.S., von Tresckow, B., Saftig, P., Rose-John, S., Engert, A., Hansen, H.P. Cancer Res. (2007) [Pubmed]
  2. Proliferation of CD30+ T-helper 2 lymphoma cells can be inhibited by CD30 receptor cross-linking with recombinant CD30 ligand. Willers, J., Dummer, R., Kempf, W., Kündig, T., Burg, G., Kadin, M.E. Clin. Cancer Res. (2003) [Pubmed]
  3. CD30L up-regulates CD30 and IL-4 expression by T cells. Rossi, F.M., Degan, M., Mazzocut-Zecchin, L., Di Francia, R., Aldinucci, D., Pinto, A., Gattei, V. FEBS Lett. (2001) [Pubmed]
  4. Co-expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) in thyroid nodules is associated with co-expression of CD30 ligand/CD30 receptor. Ruggeri, R.M., Villari, D., Simone, A., Scarfi, R., Attard, M., Orlandi, F., Barresi, G., Trimarchi, F., Trovato, M., Benvenga, S. J. Endocrinol. Invest. (2002) [Pubmed]
  5. Pleiotropic effects of the CD30 ligand on CD30-expressing cells and lymphoma cell lines. Gruss, H.J., Boiani, N., Williams, D.E., Armitage, R.J., Smith, C.A., Goodwin, R.G. Blood (1994) [Pubmed]
  6. Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion. Fischer, M., Harvima, I.T., Carvalho, R.F., Möller, C., Naukkarinen, A., Enblad, G., Nilsson, G. J. Clin. Invest. (2006) [Pubmed]
  7. Activation of HIV expression by CD30 triggering in CD4+ T cells from HIV-infected individuals. Maggi, E., Annunziato, F., Manetti, R., Biagiotti, R., Giudizi, M.G., Ravina, A., Almerigogna, F., Boiani, N., Alderson, M., Romagnani, S. Immunity (1995) [Pubmed]
  8. Cross-linking of CD30 induces HIV expression in chronically infected T cells. Biswas, P., Smith, C.A., Goletti, D., Hardy, E.C., Jackson, R.W., Fauci, A.S. Immunity (1995) [Pubmed]
  9. CD30 ligand signal transduction involves activation of a tyrosine kinase and of mitogen-activated protein kinase in a Hodgkin's lymphoma cell line. Wendtner, C.M., Schmitt, B., Gruss, H.J., Druker, B.J., Emmerich, B., Goodwin, R.G., Hallek, M. Cancer Res. (1995) [Pubmed]
  10. Role for CD30 in HIV expression. Romagnani, S., Annunziato, F., Manetti, R., Almerigogna, F., Biagiotti, R., Giudizi, M.G., Ravina, A., Giannò, V., Tomasévic, L., Maggi, E. Immunol. Lett. (1996) [Pubmed]
  11. 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]
  12. Engagement of CD153 (CD30 ligand) by CD30+ T cells inhibits class switch DNA recombination and antibody production in human IgD+ IgM+ B cells. Cerutti, A., Schaffer, A., Goodwin, R.G., Shah, S., Zan, H., Ely, S., Casali, P. J. Immunol. (2000) [Pubmed]
  13. High CD30 ligand expression by epithelial cells and Hassal's corpuscles in the medulla of human thymus. Romagnani, P., Annunziato, F., Manetti, R., Mavilia, C., Lasagni, L., Manuelli, C., Vannelli, G.B., Vanini, V., Maggi, E., Pupilli, C., Romagnani, S. Blood (1998) [Pubmed]
  14. CD30 antigen: not a physiological marker for TH2 cells but an important costimulator molecule in the regulation of the balance between TH1/TH2 response. Pellegrini, P., Berghella, A.M., Contasta, I., Adorno, D. Transpl. Immunol. (2003) [Pubmed]
  15. Human angiogenin fused to human CD30 ligand (Ang-CD30L) exhibits specific cytotoxicity against CD30-positive lymphoma. Huhn, M., Sasse, S., Tur, M.K., Matthey, B., Schinköthe, T., Rybak, S.M., Barth, S., Engert, A. Cancer Res. (2001) [Pubmed]
  16. Neonatal and adult CD4+ CD3- cells share similar gene expression profile, and neonatal cells up-regulate OX40 ligand in response to TL1A (TNFSF15). Kim, M.Y., Toellner, K.M., White, A., McConnell, F.M., Gaspal, F.M., Parnell, S.M., Jenkinson, E., Anderson, G., Lane, P.J. J. Immunol. (2006) [Pubmed]
  17. Soluble CD30 binds to CD153 with high affinity and blocks transmembrane signaling by CD30. Hargreaves, P.G., Al-Shamkhani, A. Eur. J. Immunol. (2002) [Pubmed]
  18. CD30 ligand is frequently expressed in human hematopoietic malignancies of myeloid and lymphoid origin. Gattei, V., Degan, M., Gloghini, A., De Iuliis, A., Improta, S., Rossi, F.M., Aldinucci, D., Perin, V., Serraino, D., Babare, R., Zagonel, V., Gruss, H.J., Carbone, A., Pinto, A. Blood (1997) [Pubmed]
  19. Co-expression of CD30 ligand and interleukin 4 (IL-4) receptors by acute myeloid leukaemia blasts is associated with the expansion of IL-4-producing CD30+ normal T cells. Rossi, F.M., Degan, M., Mazzocco, F.T., Di Francia, R., Aldinucci, D., Poletto, D., Vellenga, E., Pinto, A., Gattei, V. Br. J. Haematol. (2002) [Pubmed]
  20. Expression of CD40 ligand (CD154) in B and T lymphocytes of Hodgkin disease: potential therapeutic significance. Clodi, K., Asgari, Z., Younes, M., Palmer, J.L., Cabanillas, F., Carbone, A., Andreeff, M., Younes, A. Cancer (2002) [Pubmed]
  21. Expression and regulation of CD30 ligand and CD30 in human leukemia-lymphoma cell lines. Gruss, H.J., DaSilva, N., Hu, Z.B., Uphoff, C.C., Goodwin, R.G., Drexler, H.G. Leukemia (1994) [Pubmed]
  22. CD30-ligand and CD40-ligand expression in lymph nodes involved with Hodgkin's disease. Younes, A., Zhao, S., Zhang, X., Snell, V., Clodi, K., Kliche, K.O., Thomas, E., Cabanillas, F., Andreeff, M. Ann. Oncol. (1997) [Pubmed]
  23. CD30-CD30 ligand interaction in primary cutaneous CD30(+) T-cell lymphomas: A clue to the pathophysiology of clinical regression. Mori, M., Manuelli, C., Pimpinelli, N., Mavilia, C., Maggi, E., Santucci, M., Bianchi, B., Cappugi, P., Giannotti, B., Kadin, M.E. Blood (1999) [Pubmed]
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