Recombinant CD30 ligand and CD40 ligand share common biological activities on Hodgkin and Reed-Sternberg cells.
The CD30 ligand (CD30L) and CD40L are members of the tumor necrosis factor (TNF) protein superfamily, CD30L and CD40L are mainly expressed as membrane-bound proteins by activated T cells. CD30L and CD40L are costimulatory for T cell proliferation and activation. Further, CD40L is a critical signal for T cell-dependent activation of B cells. 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. We have found that both the recombinant CD30L and CD40L enhanced interleukin (IL)-6, TNF and lymphotoxin (LT)-alpha release from cultured H-RS cells. In addition, CD40L, but not CD30L, induced IL-8 secretion. CD30L and CD40L seem to share some redundant biological activities involved in the deregulated secretion of cytokines known to play a central role in the clinical presentation and pathology of HD. Further, CD30L enhanced surface expression of intercellular adhesion molecule-1 (ICAM-1/CD54) on cultured H-RS cells, which is frequently overexpressed on primary H-RS cells. CD30L- and CD40L-enhanced CD54 surface expression is followed by elevated shedding of CD54, as shown by detection of elevated 82-kDa soluble (s) CD54 levels in culture supernatants after stimulation with both ligands. CD30L and CD40L share common pleiotropic biological activities on CD30+/CD40+ H-RS cells and are elements of the cytokine and cell contact-dependent activation network typical for HD, a tumor of cytokine producing cells.
Gruss
H J
HJ
Department of Biochemistry, Immunex Research and Development Corporation, Seattle, USA.
Ulrich
D
D
Braddy
S
S
Armitage
R J
RJ
Dower
S K
SK
D053285:CD30 Ligand; D023201:CD40 Ligand; D002478:Cells, Cultured; D004357:Drug Synergism; D006689:Hodgkin Disease / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000008:administration & dosage*; D011994:Recombinant Proteins; D016539:Reed-Sternberg Cells / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D053285:CD30 Ligand; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C505774:TNFSF8 protein, human; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand