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.

CD30 triggering by agonistic antibodies regulates CXCR4 expression and CXCL12 chemotactic activity in the cell line L540.

VINANTE, Fabrizio;RIGO, Antonella;SCUPOLI, Maria;PIZZOLO, Giovanni
2002-01-01

Abstract

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.
Antibodies; Blotting, Northern; Cell Division; Cell Membrane; Chemokines, CXC; Chemotactic Factors; Chemotaxis; Cross-Linking Reagents; Hodgkin Disease; Humans; Interleukins; Ki-1 Antigen; NF-kappa B; Promoter Regions, Genetic; RNA, Messenger; Receptors, CXCR4; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; T-Lymphocytes; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured; Gene Expression Regulation
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/311281
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 24
  • ???jsp.display-item.citation.isi??? 20
social impact