EXPRESSION AND REGULATION OF CD30 LIGAND AND CD30 IN HUMAN LEUKEMIA-LYMPHOMA CELL-LINES

The CD30 antigen was originally described as a specific surface marker for Hodgkin's lymphoma. Recent work established CD30 as a member of t he tumor necrosis factor/nerve growth factor receptor superfamily whos e ligand (CD30L) has also been cloned and expressed; CD30L is active a s a membrane-bound type II glycoprotein. Here, CD30L mRNA expression w as studied in a panel of 102 continuous human leukemia-lymphoma cell l ines and was found only in four Burkitt lymphoma, one Burkitt-type acu te lymphoblastic leukemia and one non-Hodgkin's lymphoma (NHL) cell li ne. The product of CD30L mRNA is expressed as a membrane protein on th e surface of these malignant B-cell lines, Treatment of these cell lin es with soluble CD27L, phorbol ester or staphylococcus aureus Cowan an tigen resulted in the enhancement of cell surface CD30L protein expres sion. CD30L mRNA was not detected in normal unstimulated peripheral bl ood (PR) monocytes, monocyte-derived macrophages, or T-cells, but was detected in primary granulocytes; exposure to activating reagents indu ced and upregulated CD30L transcription in these different PB populati ons. While CD40 and CD30L surface protein expression on PB monocytes c ould be enhanced or induced by treatment with gamma-interferon, these cells remained negative for CD30, both at the mRNA and at the protein level. Similarly, PB monocyte-derived macrophages and granulocytes rem ained negative for CD30 mRNA and protein expression, regardless of sti mulation. Only activated T-cells expressed CD30 mRNA and surface prote in. CD30L-transfected cells and cells constitutively expressing CD30L delivered a similar stimulus for proliferation of the CD30+ Hodgkin's disease (HD)-derived cell line HDLM-2, but inhibited proliferation of the CD30+ large cell anaplastic lymphoma cell line KARPAS-299. These d ata provide strong evidence for the involvement in growth regulation o f recombinant and natural CD30L through its interaction with the CD30 receptor. Collectively, these data suggest that the CD30L-CD30 interac tion has potent biological activity and might play a critical role in the immune response and pathogenesis of HD and some NHL, in particular Burkitt lymphomas.