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Blood, 1 January 2002, Vol. 99, No. 1, pp. 52-60
CHEMOKINES
CD30 triggering by agonistic antibodies regulates CXCR4
expression and CXCL12 chemotactic activity in the cell line
L540
Fabrizio Vinante,
Antonella Rigo,
Maria Teresa Scupoli, and
Giovanni Pizzolo
From the Department of Clinical and Experimental
Medicine, Section of Hematology, University of Verona, Italy.
The tumor necrosis factor receptor family molecule CD30 is
expressed by activated and memory T cells, depending on IL-4
stimulation preferentially in association with Th0- and Th2-type
responses. It mediates pleiotropic effects primarily of the inhibitory
type. Arguing that CD30+ cells have a peculiar
redistribution in disease, it is demonstrated here, in the
Hodgkin-derived L540 cell line (an established model for studying CD30
signaling), that CD30 regulates the prototypic lymphoid chemokine
receptor CXCR4 (CD184), which plays an important role in many organ
systems and is a coreceptor for human immunodeficiency virus-1 entry.
CD30 stimulation with agonistic antibodies in L540 cells led to the
accumulation of CXCR4 mRNA, which reached a plateau after 4 hours and
did not require protein synthesis. It has been reported recently that
CD30 up-regulates the transcription of CCR7 mRNA in YT lymphoma cells.
After mRNA transcription, membrane expression of CXCR4 in L540 cells
increased as early as 12 hours, reached a plateau after 24 hours
(MFI ± SD, 839 ± 122 vs basal 168 ± 28;
P < .01) and was still increased after 5 days,
permitting enhanced sensitivity to the chemotactic activity of
CXCR4-ligand CXCL12 (CI ± SD, 10 ± 1 vs basal 5 ± 2;
P < .01). CD30 cross-linking also induced the release of
CCL5 and CCL3 and the up-regulation of membrane binding capacity for
CCL3 and CCL4 and decreased proliferative activity. This new regulatory
role of CD30 may be relevant for T-cell maturation and effector
responses and for promoting cancer biology.
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