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Recombinant CD30 ligand and CD40 ligand share common biological activities on Hodgkin and Reed-Sternberg cells
H J Gruss1, D Ulrich, S Braddy
1Department of Biochemistry, Immunex Research and Development Corporation, Seattle, USA.
Insights
Tumor necrosis factor superfamily ligands CD30L and CD40L activate Hodgkin lymphoma cells, increasing cytokine release and intercellular adhesion molecule-1 expression. These ligands contribute to the complex cytokine network in Hodgkin
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- CD30 ligand (CD30L) and CD40 ligand (CD40L) are tumor necrosis factor (TNF) superfamily members expressed on activated T cells.
- CD30L and CD40L are crucial for T cell activation and CD40L is vital for T cell-dependent B cell activation.
- Hodgkin and Reed-Sternberg (H-RS) cells, characteristic of Hodgkin's disease (HD), express CD30 and CD40 receptors.
Purpose of the Study:
- To investigate the effects of CD30L and CD40L on cytokine release and cell adhesion molecule expression in cultured H-RS cells.
- To elucidate the shared and distinct biological activities of CD30L and CD40L on H-RS cells.
- To understand the role of these ligands in the cytokine network of Hodgkin's disease.
Main Methods:
- Culturing of H-RS cells.
- Stimulation of H-RS cells with recombinant CD30L and CD40L.
- Measurement of cytokine release (IL-6, TNF, LT-alpha, IL-8) using supernatant analysis.
- Assessment of intercellular adhesion molecule-1 (ICAM-1/CD54) surface expression and shedding (soluble CD54 levels).
Main Results:
- Both CD30L and CD40L enhanced the release of IL-6, TNF, and LT-alpha from H-RS cells.
- CD40L, but not CD30L, induced IL-8 secretion.
- CD30L increased ICAM-1/CD54 surface expression on H-RS cells, leading to elevated shedding of soluble CD54.
- CD30L and CD40L exhibit overlapping biological activities on H-RS cells, contributing to the cytokine network in HD.
Conclusions:
- CD30L and CD40L share common activities on CD30+/CD40+ H-RS cells.
- These ligands are integral components of the cytokine and cell contact-dependent activation network in Hodgkin's disease.
- The findings highlight the role of TNF superfamily ligands in the pathogenesis of Hodgkin's disease.
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.