UVA1 radiation (340-400 nm) interferes with the perforin-granule system of CD8hi+ cytotoxic T lymphocytes in vitro

UVA I-irradiation was introduced as an innovative and effective phototherapy of atopic dermatitis (AD) and other skin diseases. In AD, a defect of a central apoptosis inducing effector system involved in immunoregulation and immune defense, i.e., the system of perforin-granules in cytotoxic T lymphocytes (CTL), was recently reported: perforin-reduction and perforin-hyperreleasability. We now investigated UVAI-effects on the perforin-granule system in vitro. Peripheral blood CTLs were exposed in vitro to 10-100 J/cm(2) UVAI (340-400 nm), and to 30-150 mJ/cm(2) UVB (280-315 nm) as a control. A time-dependent perforin-granule release was induced by phorbol 12-myristate 13-acetate (PMA) and ionomycin. This release was inhibited dose-dependently by UVAI, but not by UVB. An UVAI-dose dependent pattern of sensitive (80%) and insensitive (20%) individuals was found. The kinetics of perforin release in AD-CTLs, i.e. hyperreleasability, was normalized by 50 J/cm(2) UVAI in vitro. Sodium azide as a quencher of reactive oxygen species prevented the UVAI-mediated inhibition of perforin-granule release. Our data demonstrate for the first time a dose- and wavelength-dependent UVAI-effect in vitro on a major effector system of cytotoxic lymphocytes, the system of perforin-granules. This might contribute to the further understanding of immunomodulatory UVAI-effects in vivo. (C) 2006 Elsevier B.V. All rights reserved.