CD30 ligation induces nuclear factor-kappa B activation in human T cell lines.
CD30 is a recently described member of the tumor necrosis factor/nerve growth factor receptor superfamily. In this report, we show that following incubation of L540 cells (Hodgkin's disease-derived, T cell-like, CD30+ cells) with the agonistic anti-CD30 monoclonal antibodies (mAb) M44 and M67, two nuclear factor (NF)-kappa B DNA binding activities were induced in nuclear extracts, as determined in gel retardation assays. The effect of the mAb towards NF-kappa B activation was rapid, as it occurred within 20 min, and was sustained for up to 6 h. By comparison, an isotype-matched antibody had no effect on NF-kappa B activation. Moreover, in human T helper (Th) clones functionally characterized as being of the type 0, type 1 and type 2 (28%, < 1% und 93% CD30+, respectively), the extent of CD30-mediated NF-kappa B activation correlated with the proportion of CD30+ cells. In all cell lines investigated, the NF-kappa B complexes induced following CD30 engagement were shown to contain p50 NF-kappa B1, p65 RelA, and possibly other transcription factors. Collectively, our results demonstrate that nuclear translocation and activation of NF-kappa B rank among the short-term cellular responses elicited following CD30 ligation.
McDonald
P P
PP
Department of General Pathology, University of Verona, Italy.
Cassatella
M A
MA
Bald
A
A
Maggi
E
E
Romagnani
S
S
Gruss
H J
HJ
Pizzolo
G
G
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000473:pathology; D006801:Humans; D017730:Ki-1 Antigen / Q000378:metabolism*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008024:Ligands; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D017730:Ki-1 Antigen; D008024:Ligands; D016328:NF-kappa B