HYDROGEN-PEROXIDE MEDIATES UV-INDUCED IMPAIRMENT OF ANTIGEN PRESENTATION IN A MURINE EPIDERMAL-DERIVED DENDRITIC CELL-LINE

Ultraviolet-B (290-320 nm) radiation is known to impair the antigen-pr esenting cell (APC) function of Langerhans cells (LC), skin-specific m embers of the dendritic cell (DC) family. We sought to address mechani sms of this effect, focusing on the role played by hydrogen peroxide. For this purpose, we used a newly established murine DC line, XS52, wh ich resembles epidermal LC in several respects. The APC capacity of XS 52 cells, using two different CD4(+) T cell clones as responders, was inhibited significantly (>50%) by exposure to UV radiation (unfiltered FS20 sunlamps) at relatively small fluences (50-100 J/m(2)). Ultravio let radiation also inhibited growth factor-dependent proliferation of XS52 cells. On the other hand, cell surface phenotype was relatively w ell preserved after irradiation; expression levels of B7-1 and B7-2 we re reduced slightly, while other molecules (e.g. Ia, CD54, CD11a and C D18) were not affected. With respect to the role played by hydrogen pe roxide, pretreatment with purified catalase (900 U/mL) prevented UV-in duced inhibition of APC function. Short-term exposure to 3 mM H2O2 or t-butyl H2O2 mimicked UV radiation by inhibiting APC function. Finally , intrinsic catalase activity was substantially lower in XS52 cells co mpared with Pam 212 keratinocytes. These results indicate that the gen eration of hydrogen peroxide alone is sufficient to produce some, but not all, of the deleterious effects of UV radiation on DC derived from the skin.