UP-REGULATION OF HUMAN EPIDERMAL LANGERHANS CELL B7-1 AND B7-2 COSTIMULATORY MOLECULES IN-VIVO BY SOLAR-SIMULATING IRRADIATION

Ultraviolet (UV) radiation impairs cutaneous immune functions and indu ces antigen-specific tolerance both locally at the irradiated skin sit e, as well as at distant skin sites and systemically. It has been post ulated that in the local model, altered Langerhans' cells (LC) provide tolerogenic signals, and studies in vitro have indicated that UV radi ation may down-regulate the expression of costimulatory molecules on t he surface of these cells. To examine the effect of UV radiation on LC co-stimulatory molecules in vivo, we irradiated human volunteers with erythematogenic doses of solar-simulating UV radiation (SSR), and ana lyzed the expression of cell surface markers in dermatome skin samples obtained 1-72 h post-irradiation. For flow cytometric analysis, epide rmal cell (EC) suspensions were prepared and double labeled with monoc lonal antibodies against CD1a or HLA-DR, and B7-1 (CD80), B7-2 (CD86), ICAM-1 (CD54), ICAM-3 (CD50), LFA-3 (CD58), E-cadherin, or integrin-b eta(4) (CD104). In unirradiated control skin samples, keratinocytes (K C) expressed high levels of E-cadherin. LC expressed high levels of bo th E-cadherin and ICAM-3, and low levels of B7-2, LFA-3, ICAM-1, and i ntegrin-beta(4). Following SSR, a triphasic reaction pattern was seen: an immediate, down-regulatory phase prevailing 2-6 h post-irradiation , when the number of DR+ and CD1a(+) cells were temporarily reduced; a delayed, up-regulatory phase in which the number of LC was increased and the expression intensities of CD1a, HLA-DR, B7-1, and B7-2 were st rongly up-regulated, maximally evident 12-24 h after irradiation, but no more seen at 48 h; and a late phase at 72 h, in which an influx of monocytes and a concomitant rise in DR+ cells was recorded. We conclud e that to understand real-life cutaneous UV immunology, studies in vit ro need to be complemented with studies in vivo. In the case of LC, th e effects of erythematogenic UV radiation in vivo on human LC B7 co-st imulatory molecules include an up-regulatory stage.