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Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the
possible relevance for Hodgkin's disease
HJ Gruss, D Hirschstein, B Wright, D Ulrich, MA Caligiuri, M Barcos, L Strockbine, RJ Armitage and SK Dower
Department of Biochemistry, Immunex Research and Development Corp, Seattle,
WA 98101.
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.
Volume 84,
Issue 7,
pp. 2305-2314,
10/01/1994
Copyright © 1994 by The American Society of Hematology
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