Recombinant CD30 ligand and CD40 ligand share common biological activities on Hodgkin and Reed‐Sternberg cells

Abstract

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.

Expression of B7-2 (CD86) molecules by Reed–Sternberg cells of Hodgkin’s disease

“…14 LFA-3-CD2 and ICAM-1-LFA-1 interactions are thought to play a role in the stimulating capacity of these cell Discussion lines. 14,25 Looking to potential differences between B7-1 and B7-2 in providing the accessory signal, we found that B7-1 B7-1 expression on RS cells was first shown by us 14 and later confirmed by Munro et al 20 and by Gruss et al 21 In this article, was the stronger CD28 ligand for costimulation. This finding is compatible with other data that B7-1 is superior to B7-2 in we have shown that RS cells in all cases of Hodgkin's disease studied also express B7-2 molecules.…”

Spontaneous CD30 mRNA expression in peripheral blood mononuclear cells from atopic patients with high IgE serum levels

“…Furthermore, it was recently suggested that both CD30 ligand and CD40 ligand, which have an important role in IgE synthesis [29,30], may represent redundant critical elements in the cytokine and cell contact-dependent activation network for the pathology of Hodgkin's disease [23].…”

Defective IκBα in Hodgkin cell lines with constitutively active NF-κB

“…Several authors have reported the presence of CD40 on Hodgkin and Reed-Sternberg cells (Carbone et al, 1995a;Gruss et al, 1994;O'Grady et al, 1994). The number of cases expressing CD40 varied between 70% and 100% in the di erent studies, with much of this variation attributable to di erences in ®xation and the use of di erent monoclonal antibodies to CD40.…”

“…The number of cases expressing CD40 varied between 70% and 100% in the di erent studies, with much of this variation attributable to di erences in ®xation and the use of di erent monoclonal antibodies to CD40. A variety of functional e ects have been demonstrated in the Hodgkin cell lines in response to stimulation with soluble trimeric CD40-ligand (Carbone et al, 1995a;Gruss et al, 1994Gruss et al, , 1995, suggesting that the CD40 on the cell surface is competent to transduce signals following interaction with its ligand.…”