THE CD30 LIGAND AND CD40 LIGAND REGULATE CD54 SURFACE EXPRESSION AND RELEASE OF ITS SOLUBLE FORM BY CULTURED HODGKIN AND REED-STERNBERG CELLS

The membrane-bound proteins CD30 ligand (CD30L), CD40L and 4-1BBL are members of the tumor necrosis factor (TNF) superfamily. They are expre ssed mainly by activated T cells. Primary and cultured Hodgkin and Ree d-Sternberg (H-RS) cells, regarded as the malignant components of Hodg kin's disease (HD), display high levels of the counter-receptors for t hese ligands, ie CD30, CD40 and 4-1BB, CD30L and CD40L are known to sh are some biological activities that can be linked to the unbalanced se cretion of cytokines seen in HD. In addition, cell contact-dependent m olecules such as adhesion or activation antigens are critically involv ed in T cell/H-RS cell interactions. Primary and cultured H-RS cells f requently overexpress intercellular adhesion molecule-1 (ICAM-1/CD54), BB-1 (B7-1/CD80) and B70/B7-2 (CD86). Here we show that CD30L and CD4 0L, but not 4-1BBL upregulate CD54 expression by cultured H-RS cells o n the mRNA and protein level, as a result of transcriptional gene acti vation. Furthermore, enhanced CD54 surface expression by these cells i s accompanied by increased shedding of surface-bound CD54, as evidence d by high levels of the 82 kDa soluble (s) CD54 form detectable in cul ture supernatants after specific stimulation. Addition of CD30L in com bination with CD40L to cultured H-RS cells additively enhanced CD54 su rface expression and its shedding. These results may give a plausible explanation why sCD54 serum levels are increased in patients with HD.