EFFECTS OF ULTRAVIOLET-B RADIATION ON HUMAN LANGERHANS CELLS - FUNCTIONAL ALTERATION OF CD86 UP-REGULATION AND INDUCTION OF APOPTOTIC CELL-DEATH

We have recently reported that in vitro low dose of ultraviolet B radi ation (UVB, 100-200 J per m(2)) directly impaired the antigen-presenti ng function of human Langerhans cells, In this study, we analyzed the effect of WB irradiation on the Langerhans cells expression of several accessory molecules, namely CD54, CD80, and CD86, Langerhans cells ph enotype was determined either immediately after UVB exposure (100 J pe r m(2)) or after a 2 d culture. No modification in cell surface antige n levels was observed immediately after irradiation. Prior UVB exposur e did not modify the levels of CD80 at the Langerhans cells surface af ter a 2 d culture. In contrast, CD54 and, above all, CD86 expression w ere significantly decreased. Addition of exogenous anti-CD28 monoclona l antibodies partly restored the allostimulatory property of irradiate d Langerhans cells in mixed epidermal cell-lymphocyte reaction, demons trating that impairment of CD86 upregulation contributes to the UVB-in duced immunosuppressive effect. Furthermore, we found that UVB irradia tion at 200 J per m(2) significantly reduced the number of viable Lang erhans cells after 2 d of culture. UVB-induced cytotoxicity was due to apoptotic cell death, as demonstrated by typical morphologic alterati ons and by DNA fragmentation yielding a classical ladder pattern on ge l electrophoresis, Interestingly, interaction of Langerhans cells with CD40-ligand transfected L cells improved the viability of irradiated Langerhans cells, counteracted the inhibition of CD86 expression, and efficiently reduced the number of apoptotic cells after a 2 d culture. Collectively, these results demonstrate that in vitro UVB exposure af fects Langerhans cells via at least two distinct pathways: (i) decreas ed CD86 costimulatory molecule upregulation; and (ii) induction of Lan gerhans cells apoptosis, a phenomenon partly prevented by CD40 trigger ing.