Different susceptibility of malignant versus nonmalignant human T cells toward ultraviolet A-1 radiation-induced apoptosis.
Ultraviolet (UV) A-1 (340-400 nm) radiation is highly effective in inducing apoptosis in skin-infiltrating T cells and thereby exerts beneficial effects in patients with T cell-mediated skin diseases. In this in vitro study, we report that malignant and normal T cells differ in their susceptibility toward UVA-1 radiation-induced apoptosis. Dose-response studies revealed that malignant CD4+ T cells isolated from a patient with adult T cell leukemia and Sezary's syndrome as well as malignant T cell lines exhibited a significantly higher susceptibility toward UVA-1 radiation-induced apoptosis 4 h (early apoptosis) and 24 h (late apoptosis) after exposure than normal, CD4+ T cells. This difference was specific for UVA-1 irradiation because it was not detected when apoptosis was induced in these cells through exposure to UVB radiation or stimulation with cell-permeable ceramides. It has been shown that UVA-1 radiation-induced T cell apoptosis is initiated through the generation of singlet oxygen. This is in agreement with the present observation that stimulation of unirradiated cells with a singlet oxygen-generating system induced apoptosis in malignant cells to a greater extent than in normal cells. Moreover, downregulation of FAS surface expression in malignant T cells was associated with the inhibition of UVA-1 radiation/singlet oxygen-induced apoptosis in these cells. It was thus of great interest to learn that addition of the caspase inhibitor Z-VADfmk decreased and interferon-gamma stimulation, which is known to upregulate caspase levels including caspase-3, increased the sensitivity of T cells toward UVA-1 radiation-induced apoptosis. Furthermore, malignant T cells had significantly higher procaspase-3 levels when compared with normal cells. These studies indicate that the susceptibility of human T cells toward UVA-1 radiation-induced apoptosis is related to the availability of caspases such as caspase-3 and that strategies directed at upregulating caspase levels will increase the efficacy of UVA-1 phototherapy.
Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Ritsuko
R
Yamauchi
Akimichi
A
Morita
Yoko
Y
Yasuda
Susanne
S
Grether-Beck
Lars-Oliver
LO
Klotz
Takuo
T
Tsuji
Jean
J
Krutmann
D017209:Apoptosis / Q000528:radiation effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D015458:Leukemia, T-Cell; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000528:radiation effects*; D014466:Ultraviolet Rays
C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases