title: UVA1 radiation (340-400 nm) interferes with the perforin-granule system of CD8hi+ cytotoxic T lymphocytes in vitro.
abstract: UVA1-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 UVA1-effects on the perforin-granule system in vitro. Peripheral blood CTLs were exposed in vitro to 10-100 J/cm2 UVA1 (340-400 nm), and to 30-150 mJ/cm2 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 UVA1, but not by UVB. An UVA1-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/cm2 UVA1 in vitro. Sodium azide as a quencher of reactive oxygen species prevented the UVA1-mediated inhibition of perforin-granule release. Our data demonstrate for the first time a dose- and wavelength-dependent UVA1-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 UVA1-effects in vivo.
authors.affiliation: Clinic of Dermatology and Venereology, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany. Andreas.Ambach@Medizin.Uni-Magdeburg.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Ambach
authors.forename: Bernd
authors.initials: B
authors.lastname: Bonnekoh
authors.forename: Harald
authors.initials: H
authors.lastname: Gollnick
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects*; D003594:Cytoplasmic Granules / Q000276:immunology / Q000528:radiation effects*; D006801:Humans; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D019810:Sodium Azide / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D015759:Ionomycin; D019810:Sodium Azide; D013755:Tetradecanoylphorbol Acetate