Disease relevance of TNFSF8

• 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 [1].
• PURPOSE: Cutaneous anaplastic large cell lymphomas (ALCLs) are characterized by the expression of CD30, spontaneous regression of skin lesions, and increased concentration of CD30 ligand (CD30L) [2].
• CD30L is frequently expressed on acute myeloid leukemia (AML) blasts [3].
• IL-6 staining associated to absent expression of CD30L and CD30 was observed in 7 follicular adenomas (all belonging to variants different from toxic and hyalinizing trabecular), 2 oncocytic adenomas, 5 of the 30 colloid nodules and 2 normal thyroids [4].
• Recombinant CD30 ligand enhanced proliferation of "T-cell-like" Hodgkin's disease-derived cell lines and an adult T-cell leukemia cell line, but not "B-cell-like" Hodgkin's disease-derived cell lines, CD30+, EBV-immortalized lymphoblastoid B-cell lines, or CD30+ and EBV+ tumor B-cell non-Hodgkin's lymphoma cell lines [5].
• Mast cells were found to be the predominant CD30 ligand-positive (CD30L-positive) cell in the chronic inflammatory skin diseases psoriasis and atopic dermatitis, and both CD30 and CD30L expression were upregulated in lesional skin in these conditions [6].

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

• CD30 ligand signal transduction involves activation of a tyrosine kinase and of mitogen-activated protein kinase in a Hodgkin's lymphoma cell line [9].
• More importantly, paraformaldehyde-fixed CD8+ T-cell clones expressing CD30L enhanced HIV replication in anti-CD3-stimulated allogeneic or autologous HIV-infected CD4+ T-cell lines and such a potentiating effect was inhibited by an anti-CD30L antibody [10].

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

• We conclude that only in a subset of both benign and malignant thyroid nodules the IL-6/IL-6R signal could be induced by the CD30L/CD30 [4].
• CD30 ligand is frequently expressed in human hematopoietic malignancies of myeloid and lymphoid origin [18].

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

• The expression levels of CD30 were assessed by flow cytometry [2].
• CONCLUSIONS: CD30+ ALCL cells can be growth inhibited by receptor ligation [2].
• The affinity and kinetics of the interaction between soluble CD30 and CD153 were determined using the BIAcore biosensor [17].
• Messenger RNA expression of CD30L and CD40L was determined by the reverse-transcriptase polymerase chain reaction (RT-PCR) method performed on seven specimens involved with Hodgkin's disease (five lymph nodes and two spleens) [22].
• By immunohistochemistry, CD30L expression was detected in regressing lesions only; by molecular analysis, the expression of CD30L was clearly higher in regressing lesions than in growing ones [23].

References