EXPRESSION AND FUNCTION OF CD40 ON HODGKIN AND REED-STERNBERG CELLS AND THE POSSIBLE RELEVANCE FOR HODGKINS-DISEASE

CD40 was originally described as a B-cell-restricted antigen and was s ubsequently found to be a member of the tumor necrosis factor (TNF) re ceptor superfamily. CD40 is also expressed on dendritic cells, thymic epithelium, monocytes, and some carcinoma cell lines, and plays a crit ical role in cell contact-dependent activation. Primary and cultured H odgkin and Reed-Sternberg (H-RS) cells, the presumed malignant cells o f Hodgkin's disease (HD), were found to express high levels of cell su rface CD40. We found that recombinant CD40 ligand (CD40L) induced inte rleukin-8 (IL-8) secretion and enhanced IL-6, TNF, and lymphotoxin-alp ha (LT-alpha/TNF-beta) release from cultured H-RS cells. These cytokin es play a significant role in the clinical presentation and pathology of HD, a tumor of cytokine-producing cells. CD40L had no mitogenic act ivity for HD-derived cell lines. In contrast, CD40L enhanced expressio n 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 ex pression 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-R S cells, and the CD40-CD40L interaction might be a critical element in the deregulated cytokine network and cell contact-dependent activatio n cascade typical for HD. (C) 1994 by The American Society of Hematolo gy.