1. ^*Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
2. ^†Institut für Umweltmedizinische Forschung (IUF), Heinrich-Heine-University, Düsseldorf, Germany
3. ^‡Institut für Physiologische Chemie I, Heinrich-Heine-University, Düsseldorf, Germany
4. ^§Biologisch-Medizinisches Forschungszentrum (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany

Correspondence: Akimichi Morita, MD, PhD., Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan. Email: amorita@med.Nagoya-cu.ac.jp

Received 19 February 2003; Revised 27 July 2003; Accepted 14 August 2003; Published online 12 February 2004.

Abstract

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- 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.