Proliferation of CD30+ T-helper 2 lymphoma cells can be inhibited by CD30 receptor cross-linking with recombinant CD30 ligand.
OBJECTIVE
Cutaneous anaplastic large cell lymphomas (ALCLs) are characterized by the expression of CD30, spontaneous regression of skin lesions, and increased concentration of CD30 ligand (CD30L). We hypothesize that CD30-CD30L interactions explain the unusual clinical behavior of cutaneous ALCLs.


METHODS
Eight lymphoma cell lines established from four different patients were analyzed for T-cell clonality using PCR and subsequently denaturating gradient gel electrophoresis. The expression levels of CD30 were assessed by flow cytometry. Secreted cytokines [IFN-gamma, interleukin (IL)-2, IL-4, IL-6, IL-8, and IL-10] were determined in the supernatant after 3-day culture. Proliferation and apoptosis of cultured cells were measured by 5-bromo-2-desoxyuridine and propidium iodine incorporation.


RESULTS
The results showed different levels of CD30 expression and a predominant T-helper 2 profile. In a cell kinetic analysis we found that ALCL cell growth is effectively inhibited by CD30L but only in those cell lines expressing CD30 molecules in sufficient amounts on the cell surface. Cell cycle analysis revealed that growth regulation was because of apoptosis and growth arrest, and was dependent on cell culture conditions. Comparison of effects of ligation with CD30L and anti-CD30 agonistic antibody HeFi-1 revealed higher efficacy for CD30L in these ALCL lines.


CONCLUSIONS
CD30+ ALCL cells can be growth inhibited by receptor ligation. Observed pleiotropic effects of CD30 signaling are most likely dependent on cell cycle status and signal strength. The binding of CD30 by its ligand provides new opportunities for controlling cell growth and treatment of CD30+ ALCL.
Willers
Jörg
J
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Dummer
Reinhard
R
Kempf
Werner
W
Kündig
Thomas
T
Burg
Günter
G
Kadin
Marshall E
ME
D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000494:pharmacology; D053285:CD30 Ligand; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D017730:Ki-1 Antigen / Q000096:biosynthesis*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011419:Propidium / Q000494:pharmacology; D011485:Protein Binding; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D015398:Signal Transduction; D018418:Th2 Cells / Q000378:metabolism*; D013997:Time Factors
D053285:CD30 Ligand; D016207:Cytokines; D017730:Ki-1 Antigen; D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C505774:TNFSF8 protein, human; D011419:Propidium; D004247:DNA; D001973:Bromodeoxyuridine