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Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for hodgkin's disease

Item Type:Article
Title:Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for hodgkin's disease
Creators Name:Gruss, H.J. and Hirschstein, D. and Wright, B. and Ulrich, D. and Caliguri, M.A. and Strockbine, L. and Armitage, R.J. and Dower, S.K.
Abstract: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-alpha (LT-alpha/TNF-beta) 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-T 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.
Keywords:CD Antigens, B-Lymphocyte Differentiation Antigens, CD40 Ligand, Gene Expression, Hodgkin Disease, Intercellular Adhesion Molecule-1, Diffuse Large B-Cell Lymphoma, Membrane Glycoproteins, Messenger RNA, Neoplasm RNA, Reed-Sternberg Cells, Cultured Tumor Cells
Publisher:American Society of Hematology
Page Range:2305-2314
Date:1 October 1994
Official Publication:http://bloodjournal.hematologylibrary.org/cgi/content/abstract/84/7/2305
PubMed:View item in PubMed

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