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Gene Review

Tnfrsf8  -  tumor necrosis factor receptor superfamily...

Mus musculus

Synonyms: CD30, CD30L receptor, Cd30, D1S166E, Ki, ...
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Disease relevance of Tnfrsf8


High impact information on Tnfrsf8

  • We report here that the thymus in CD30-deficient mice contains elevated numbers of thymocytes [3].
  • Thus, like TNF-receptors and Fas/Apo-1, the CD30 receptor is involved in cell death signaling [3].
  • Here we describe a new mechanism that protects against autoimmunity: this mechanism involves another member of this superfamily, CD30, whose function was largely unknown [4].
  • CD30-deficient islet-specific CD8-positive T cells are roughly 6,000-fold more autoaggressive than wild-type cells, with the transfer of as few as 160 CD30-deficient T cells leading to the complete destruction of pancreatic islets and the rapid onset of diabetes [4].
  • CD4(+)CD3(-) accessory cells costimulate primed CD4 T cells through OX40 and CD30 at sites where T cells collaborate with B cells [5].

Chemical compound and disease context of Tnfrsf8

  • We describe the in vitro and in vivo properties of monoclonal antibody (mAb)-drug conjugates consisting of the potent synthetic dolastatin 10 analogs auristatin E (AE) and monomethylauristatin E (MMAE), linked to the chimeric mAbs cBR96 (specific to Lewis Y on carcinomas) and cAC10 (specific to CD30 on hematological malignancies) [6].
  • PURPOSE: To develop a novel targeting reagent to CD30 expressed on Hodgkin'sdisease and anaplastic large cell lymphoma, we made a panel of recombinant immunotoxins specific for CD30 using Fvs of newly produced anti-CD30 monoclonal antibodies (MAbs) and a M(r) 38,000 truncated mutant of Pseudomonas exotoxin [7].

Biological context of Tnfrsf8


Anatomical context of Tnfrsf8

  • A novel role of CD30/CD30 ligand signaling in the generation of long-lived memory CD8+ T cells [1].
  • CD30-deficient mice showed an impaired capacity to sustain follicular germinal center responses, and recall memory Ab responses were substantially reduced [12].
  • Although some TNFR-related molecules are constitutively expressed, others, such as CD30 and Ox40, are induced upon activation of lymphocytes [13].
  • We show that, in the absence of CD30 signalling, cells activated but not yet deleted by the CD95-dependent cross-tolerance mechanism gain the ability to proliferate extensively upon secondary encounter with antigen on parenchymal tissues, such as the pancreatic islets [4].
  • Chromosomal translocation t(2;5) and the resulting fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) are detected in 50% to 70% of anaplastic large cell lymphoma (ALCL), which is a T/null cell non-Hodgkin's lymphoma showing anaplastic morphology with cell surface expression of CD30 [14].

Associations of Tnfrsf8 with chemical compounds

  • In vitro, in the absence of CD30 ligation, thymocytes of CD30 Tg mice have normal survival and responses to apoptotic stimuli such as radiation, dexamethasone, and Fas [15].
  • Ki-A10-negative cells were treated with 5-aza-2'-deoxycytidine [16].
  • AdoHcy and c3AdoHcy were found to be competitive inhibitors (with Ki values of 1.7 and 4.8 mM, respectively) of the high-affinity cyclic AMP phosphodiesterase present in lymphocyte homogenates [17].
  • One with high affinity for cyclic GMP was strongly inhibited (Ki = 10 microM) by NPT 15392 [18].
  • The isoquinolinesulfonamide PKC inhibitors H-7 and H-8 inhibit primary, in vivo generated cytotoxic T lymphocyte (CTL) activity by 50% at concentrations approximating their reported Ki values for PKC, 6 uM and 15 uM respectively [19].

Regulatory relationships of Tnfrsf8

  • The pleiotropic functions of CD30 are initiated by interaction of CD30-expressing cells with other immune competent cells expressing CD30-L and providing the signals for modulation of effector cell activity [20].
  • These results suggest a role for CD30 in regulating the onset of apoptosis in CD8 T cells after interruption of CD3/TCR [21].
  • In this study, we report that unlike CD28, ligation of CD30 on normal effector T cells induces IL-13 production in the absence of concurrent TCR engagement [22].

Other interactions of Tnfrsf8


Analytical, diagnostic and therapeutic context of Tnfrsf8

  • CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism [10].
  • The immunoprecipitation study with 3G12 demonstrated a major band of 200 kD and a minor band of 100 kD, which were different from CD30 [24].
  • The chimeric anti-CD30 IgG1, cAC10, conjugated to eight equivalents of monomethyl auristatin E (MMAE) was previously shown to have potent antitumor activity against CD30-expressing tumors xenografts in mice [25].
  • To overcome shedding-dependent damage of normal cells in CD30-specific immunotherapy, we analyzed the mechanism involved in the release [26].
  • In coculture experiments, the antibody-induced transfer of sCD30 from the human Hodgkin's lymphoma cell line L540 to the CD30-negative but CD153-expressing human mast cell line HMC-1 was inhibited by GI254023X [26].


  1. A novel role of CD30/CD30 ligand signaling in the generation of long-lived memory CD8+ T cells. Nishimura, H., Yajima, T., Muta, H., Podack, E.R., Tani, K., Yoshikai, Y. J. Immunol. (2005) [Pubmed]
  2. Contribution of CD30/CD153 but not of CD27/CD70, CD134/OX40L, or CD137/4-1BBL to the optimal induction of protective immunity to Mycobacterium avium. Flórido, M., Borges, M., Yagita, H., Appelberg, R. J. Leukoc. Biol. (2004) [Pubmed]
  3. Impaired negative selection of T cells in Hodgkin's disease antigen CD30-deficient mice. Amakawa, R., Hakem, A., Kundig, T.M., Matsuyama, T., Simard, J.J., Timms, E., Wakeham, A., Mittruecker, H.W., Griesser, H., Takimoto, H., Schmits, R., Shahinian, A., Ohashi, P., Penninger, J.M., Mak, T.W. Cell (1996) [Pubmed]
  4. Signalling through CD30 protects against autoimmune diabetes mediated by CD8 T cells. Kurts, C., Carbone, F.R., Krummel, M.F., Koch, K.M., Miller, J.F., Heath, W.R. Nature (1999) [Pubmed]
  5. CD4(+)CD3(-) accessory cells costimulate primed CD4 T cells through OX40 and CD30 at sites where T cells collaborate with B cells. Kim, M.Y., Gaspal, F.M., Wiggett, H.E., McConnell, F.M., Gulbranson-Judge, A., Raykundalia, C., Walker, L.S., Goodall, M.D., Lane, P.J. Immunity (2003) [Pubmed]
  6. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Doronina, S.O., Toki, B.E., Torgov, M.Y., Mendelsohn, B.A., Cerveny, C.G., Chace, D.F., DeBlanc, R.L., Gearing, R.P., Bovee, T.D., Siegall, C.B., Francisco, J.A., Wahl, A.F., Meyer, D.L., Senter, P.D. Nat. Biotechnol. (2003) [Pubmed]
  7. Novel anti-CD30 recombinant immunotoxins containing disulfide-stabilized Fv fragments. Nagata, S., Onda, M., Numata, Y., Santora, K., Beers, R., Kreitman, R.J., Pastan, I. Clin. Cancer Res. (2002) [Pubmed]
  8. CD30/CD30 ligand (CD153) interaction regulates CD4+ T cell-mediated graft-versus-host disease. Blazar, B.R., Levy, R.B., Mak, T.W., Panoskaltsis-Mortari, A., Muta, H., Jones, M., Roskos, M., Serody, J.S., Yagita, H., Podack, E.R., Taylor, P.A. J. Immunol. (2004) [Pubmed]
  9. Regulation of murine B cell growth and differentiation by CD30 ligand. Shanebeck, K.D., Maliszewski, C.R., Kennedy, M.K., Picha, K.S., Smith, C.A., Goodwin, R.G., Grabstein, K.H. Eur. J. Immunol. (1995) [Pubmed]
  10. CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism. Dai, Z., Li, Q., Wang, Y., Gao, G., Diggs, L.S., Tellides, G., Lakkis, F.G. J. Clin. Invest. (2004) [Pubmed]
  11. Marek's disease is a natural model for lymphomas overexpressing Hodgkin's disease antigen (CD30). Burgess, S.C., Young, J.R., Baaten, B.J., Hunt, L., Ross, L.N., Parcells, M.S., Kumar, P.M., Tregaskes, C.A., Lee, L.F., Davison, T.F. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  12. Mice deficient in OX40 and CD30 signals lack memory antibody responses because of deficient CD4 T cell memory. Gaspal, F.M., Kim, M.Y., McConnell, F.M., Raykundalia, C., Bekiaris, V., Lane, P.J. J. Immunol. (2005) [Pubmed]
  13. Expression of CD30 and Ox40 on T lymphocyte subsets is controlled by distinct regulatory mechanisms. Toennies, H.M., Green, J.M., Arch, R.H. J. Leukoc. Biol. (2004) [Pubmed]
  14. The Expression of CD30 in Anaplastic Large Cell Lymphoma Is Regulated by Nucleophosmin-Anaplastic Lymphoma Kinase-Mediated JunB Level in a Cell Type-Specific Manner. Hsu, F.Y., Johnston, P.B., Burke, K.A., Zhao, Y. Cancer Res. (2006) [Pubmed]
  15. CD30 overexpression enhances negative selection in the thymus and mediates programmed cell death via a Bcl-2-sensitive pathway. Chiarle, R., Podda, A., Prolla, G., Podack, E.R., Thorbecke, G.J., Inghirami, G. J. Immunol. (1999) [Pubmed]
  16. Characterization and expression of CT45 in Hodgkin's lymphoma. Heidebrecht, H.J., Claviez, A., Kruse, M.L., Pollmann, M., Buck, F., Harder, S., Tiemann, M., Dörffel, W., Parwaresch, R. Clin. Cancer Res. (2006) [Pubmed]
  17. Modulation of cyclic AMP metabolism by S-adenosylhomocysteine and S-3-deazaadenosylhomocysteine in mouse lymphocytes. Zimmerman, T.P., Schmitges, C.J., Wolberg, G., Deeprose, R.D., Duncan, G.S., Cuatrecasas, P., Elion, G.B. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  18. Selective inhibition by NPT 15392 of lymphocyte cyclic GMP phosphodiesterase. Coffey, R.G., Hartley, L., Polson, J.B., Krzanowski, J.J., Hadden, J.W. Biochem. Pharmacol. (1984) [Pubmed]
  19. Protein kinase C (PKC) inhibitors inhibit primary (1-0) but not secondary (1-1) or cloned cytotoxic T lymphocytes. Howcroft, T.K., Tatum, S.M., Cosgrove, J.M., Lindquist, R.R. Biochem. Biophys. Res. Commun. (1988) [Pubmed]
  20. Regulation of lymphocyte clustering by CD30-mediated ICAM-1 up-regulation. Nam, S.Y., Cho, K.S., Heo, Y.M., Ha, J.C., Kim, Y.H., Keun Yi, H., Han Hwang, P., Kim, H.M., Podack, E.R. Cell. Immunol. (2002) [Pubmed]
  21. CD30-regulated apoptosis in murine CD8 T cells after cessation of TCR signals. Telford, W.G., Nam, S.Y., Podack, E.R., Miller, R.A. Cell. Immunol. (1997) [Pubmed]
  22. TCR-independent CD30 signaling selectively induces IL-13 production via a TNF receptor-associated factor/p38 mitogen-activated protein kinase-dependent mechanism. Harlin, H., Podack, E., Boothby, M., Alegre, M.L. J. Immunol. (2002) [Pubmed]
  23. Analysis of the mouse CD30 gene: a candidate for the NOD mouse type 1 diabetes locus Idd9.2. Siegmund, T., Armitage, N., Wicker, L.S., Peterson, L.B., Todd, J.A., Lyons, P.A. Diabetes (2000) [Pubmed]
  24. A monoclonal antibody, 3G12, reacts with a novel surface molecule, Hal-1, with high expression in CD30-positive anaplastic large cell lymphomas. Asanuma, H., Takahashi, S., Ishikawa, M., Kamiguchi, K., Sato, N., Poppema, S., Fujimoto, J.I., Kikuchi, K. Br. J. Haematol. (1999) [Pubmed]
  25. Engineered antibody-drug conjugates with defined sites and stoichiometries of drug attachment. McDonagh, C.F., Turcott, E., Westendorf, L., Webster, J.B., Alley, S.C., Kim, K., Andreyka, J., Stone, I., Hamblett, K.J., Francisco, J.A., Carter, P. Protein Eng. Des. Sel. (2006) [Pubmed]
  26. 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]
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