Expression and Function of CD40 on Hodgkin and Reed-Sternberg Cells and the Possible Relevance for Hodgkin's Disease

• Published in: Blood 1994-10, Vol.84 (7), p.2305-2314
• Main Authors: Gruss, Hans-Jurgen, Hirschstein, Daniel, Wright, Barbara, Ulrich, Dawn, Caligiuri, Michael A., Barcos, Maurice, Strockbine, Laura, Armitage, Richard J., Dower, Steven K.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens, CD - metabolism; Antigens, Differentiation, B-Lymphocyte - metabolism; B7-1 Antigen - metabolism; CD40 Antigens; CD40 Ligand; Female; Gene Expression; Hodgkin Disease - immunology; Humans; In Vitro Techniques; Intercellular Adhesion Molecule-1 - metabolism; Ki-1 Antigen - metabolism; Lymphoma, Large B-Cell, Diffuse - immunology; Male; Membrane Glycoproteins - metabolism; Reed-Sternberg Cells - immunology; RNA, Messenger - genetics; RNA, Neoplasm - genetics; Tumor Cells, Cultured
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V84.7.2305.2305

CD40 was originally described as a B-cell–restricted antigen and was subsequently found to be a member of the tumor necrosis factor (TNF) receptor superfamily. CD40 is also expressed on dendritic cells, thymic epithelium, monocytes, and some carcinoma cell lines, and plays a critical role in cell contact-dependent activation. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the presumed malignant cells of Hodgkin's disease (HD), were found to express high levels of cell surface CD40. We found that recombinant CD40 ligand (CD40L) induced interleukin-8 (IL-8) secretion and enhanced IL-6, TNF, and lymphotoxin-α (LT-α/TNF-β) release from cultured H-RS cells. These cytokines play a significant role in the clinical presentation and pathology of HD, a tumor of cytokine-producing cells. CD40L had no mitogenic activity for HD-derived cell lines. In contrast, CD40L enhanced expression of costimulatory molecules intracellular adhesion molecule-1 and B7-1 on cultured H-RS cells, both of which are overexpressed on primary H-RS cells. In addition, CD40L induced a 40% to 60% reduction of the expression of the HD-associated CD30 antigen, another member of the TNF receptor superfamily. Primary and cultured H-RS cells express not only CD30, but also CD40. CD40L has pleiotropic biologic activities on H-RS cells, and the CD40-CD40L interaction might be a critical element in the deregulated cytokine network and cell contact-dependent activation cascade typical for HD.