Disease relevance of TNFRSF8

• Ligation of CD30 was previously shown to induce NF-kappaB activation and HIV expression in chronically infected T lymphocytes [1].
• CD30 is a lymphoid cell-specific surface receptor which was originally identified as an antigen expressed on Hodgkin's lymphoma cells [2].
• Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the neoplastic component of Hodgkin's disease (HD), express high levels of the counterreceptors CD30 and CD40 [3].
• Single-cell analysis of CD30+ cells in lymphomatoid papulosis demonstrates a common clonal T-cell origin [4].
• We identified and cloned cDNAs for two novel CD30 mRNAs of 2.3 kb that are induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in the human myeloid leukemia cell line HL-60 [5].

High impact information on TNFRSF8

• We isolated single Reed-Sternberg cells from frozen sections that had been immunostained for CD30 [6].
• In order to contribute to the characterization of the molecular mechanisms of this disease, cDNAs coding for the HD characteristic antigen CD30 were cloned from expression libraries of the human HUT-102 cell line using the monoclonal antibodies Ki-1 and Ber-H2 [7].
• When expressed in COS-1 cells, the cDNA presented properties comparable to native CD30 antigen [7].
• Bispecific monoclonal antibodies (Bi-mAbs) were designed that bound to a Hodgkin's tumor-associated antigen (CD30) on the tumor and to either CD3 or CD28 on the T cell [8].
• Thus, CD30 triggering by CD30L-expressing cells may plan an important role in the activation of HIV expression from latently infected CD4+ T cells [9].

Chemical compound and disease context of TNFRSF8

• The tyrosine kinase NPM-ALK, associated with anaplastic large cell lymphoma, binds the intracellular domain of the surface receptor CD30 but is not activated by CD30 stimulation [10].
• CD30 is a member of the tumor necrosis factor (TNF) receptor superfamily that is expressed on activated lymphocytes, as well as on neoplastic cells of Hodgkin disease (HD) and anaplastic large cell lymphoma (ALCL) [11].
• Induction of cell cycle arrest and apoptosis by the proteasome inhibitor PS-341 in Hodgkin disease cell lines is independent of inhibitor of nuclear factor-kappaB mutations or activation of the CD30, CD40, and RANK receptors [12].
• Cell-surface expression of CD25, CD26, and CD30 by allergen-specific T cells is intrinsically different in cow's milk allergy [13].
• Sections from formalin-fixed, paraffin-embedded tissue from 38 cases of testicular seminomas were immunostained for the demonstration of the CD30 antigen using the monoclonal antibody Ber-H2, cytokeratins, and placental alkaline phosphatase following an indirect streptavidin-peroxidase regimen [14].

Biological context of TNFRSF8

• CD30v can activate the nuclear factor-kappaB (NF-kappaB) as CD30, and its overexpression in HL-60 induced a differentiated phenotype [15].
• CD30 contains two binding sites with different specificities for members of the tumor necrosis factor receptor-associated factor family of signal transducing proteins [16].
• However, little is known about CD30 signal transduction [16].
• Analysis of the ICAM-1 promoter showed the importance of NF-kappaB binding site for CD30-induced ICAM-1 gene expression [17].
• Transactivation of the ICAM-1 gene by CD30 in Hodgkin's lymphoma [17].

Anatomical context of TNFRSF8

• CD30 is a member of the tumor necrosis factor receptor (TNFR) superfamily expressed on activated T and B lymphocytes and natural killer cells [1].
• 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 [18].
• CD30 can regulate proliferation of lymphocytes and may also play an important role in human immunodeficiency virus replication [16].
• BACKGROUND: Reed-Sternberg cells of Hodgkin's disease express CD30 and CD40 receptors [19].
• High levels of soluble CD30 (sCD30) were detected in the serum and synovial fluid of patients with rheumatoid arthritis (RA), indicating the involvement of CD30+ T cells in the pathogenesis [20].

Associations of TNFRSF8 with chemical compounds

• CD30 ligand (CD30L) is a type-II membrane glycoprotein capable of transducing signals leading to either cell death or proliferation through its specific counterstructure CD30 [21].
• Translation of these transcripts appeared to start from the internal methionine codon at nucleotide position 289 that corresponds to that of 1612 in the CD30 cDNA, and encode a protein of 132 amino acid residues which corresponds exactly to the C-terminal cytoplasmic domain of CD30 protein [5].
• Percentage of apoptotic eosinophils was determined by annexin V-propidium iodide labeling, and CD30 expression was examined by flow cytometry [22].
• Activation of CD30 neither enhanced NPM-ALK activity measured by autophosphorylation of the chimeric tyrosine kinase nor phosphorylation of phospholipase C-gamma, an NPM-ALK substrate [10].
• CD30-dependent cell proliferation and activation was analyzed by applying the trypan blue exclusion method and a luciferase-based ATP assay [23].

Physical interactions of TNFRSF8

• The TRAF-binding domain of CD30 was mapped to the COOH-terminal 36 amino acid residues, which contained two independent binding sites [16].
• Soluble CD30 binds to CD153 with high affinity and blocks transmembrane signaling by CD30 [24].

Regulatory relationships of TNFRSF8

• These results suggest involvement of TRAF protein aggregation in the signaling process of highly expressed CD30 and suggest they function as scaffolding proteins [25].
• CD30 induced ICAM-1 expression [17].
• CD30L up-regulates CD30 and IL-4 expression by T cells [26].
• CD4+ T cells from both the peripheral blood (PB) and synovial tissue (ST) of RA patients expressed surface CD30 when stimulated with anti-CD3 antibody (Ab) and anti-CD28 Ab, but their CD30 induction was slower and weaker compared with PB CD4+ T cells of healthy controls (HC) [20].
• Cross-linking of CD30 promotes rapid and transient binding activity of nuclear proteins to the NF-kappabeta recognition site of the IL-6 promoter [27].
• CD30 stimulation of ALCL cells activated nuclear transcription factor-kappaB (NF-kappaB), induced major transcriptional changes, and decreased proliferation [28].

Other interactions of TNFRSF8

• Domain 2 contains two 5- to 10-amino-acid elements which can mediate the binding of CD30 to members of the tumor necrosis factor receptor-associated factor (TRAF) family of signal transducing proteins [2].
• All these phenomena have also been observed in the TNF receptor type II, CD30 and CD40 signaling system, indicating that this receptor family uses the common or similar molecules for this signal [29].
• CD30 is a member of the tumor necrosis factor (TNF) receptor family of proteins [16].
• Deletion analysis by the yeast two-hybrid system revealed that the C-terminal 22 and 30 amino acid residues are dispensable for interaction of TRAF5 and TRAF2 with CD30, respectively [30].
• CD30 ligand (CD30L), but not its cognate receptor CD30, is frequently expressed on acute myeloid leukaemia (AML) blasts [31].

Analytical, diagnostic and therapeutic context of TNFRSF8

• To overcome shedding-dependent damage of normal cells in CD30-specific immunotherapy, we analyzed the mechanism involved in the release [18].
• Confocal immunofluorescence microscopy of cell lines derived from H-RS cells and HEK293 transformants highly expressing CD30 revealed aggregation of TRAF2 and TRAF5 in the cytoplasm as well as clustering near the cell membrane [25].
• Immunoblotting analysis with HCD30C1, a rabbit polyclonal antibody raised against the cytoplasmic domain of CD30 protein, detected proteins with an apparent Mr 25 kD expressed in TPA-stimulated HL-60 and COS-7 cells that were transfected with both types of CD30v cDNAs [5].
• Furthermore, CD30 expression marked the predominant proliferating T cell population induced by alloantigen as determined by CFSE staining and flow cytometry [32].
• We also measured CD30 mRNA expression by quantitative real-time RT-PCR and determined that CD30 transcripts increased in eosinophils undergoing apoptosis only under serum deprivation conditions [22].

References