OX40 signaling renders adult T-cell leukemia cells resistant to Fas-induced apoptosis.
We reported previously that OX40, a member of the tumor necrosis factor receptor family, is expressed constitutively on fresh leukemia/lymphoma cells isolated from patients with adult T-cell leukemia (ATL). In this study, we tested whether OX40 signaling affects the Fas-mediated apoptosis of fresh ATL cells isolated from 7 patients (3 acute type, 3 chronic type, and 1 smoldering type). In all these patients, the coculture of ATL cells with MMCE/OX40 ligand gp34, a stable human gp34 transfectant of a mouse epithelial cell line, resulted in a decrease in the percentage of apoptotic cells after treatment with anti-Fas monoclonal antibody, compared to coculture with MMCE/mock controls. Similar findings were obtained in OX40(+)- human T-cell leukemia virus type I-transformed T-cell lines. To elucidate the molecular mechanism of this phenomenon, we used Kit225/OX40, a stable OX40 transfectant of an IL-2-dependent T-cell line, and its deletion mutant, Kit225/del-OX40, in which the intracytoplasmic domain of OX40 had been deleted. Coculture with MMCE/gp34 inhibited the apoptosis of Kit225/OX40, but Kit225/del-OX40 apoptosis was hardly affected. These results suggest that ATL cells may escape Fas-mediated destruction of the immune system through OX40 signaling.
Kunitomi
Akane
A
Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Sakyo, Japan.
Hori
Toshiyuki
T
Maeda
Michiyuki
M
Uchiyama
Takashi
T
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000494:pharmacology*; D019014:fas Receptor / Q000494:pharmacology*
D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C505717:Tnfrsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019014:fas Receptor