The major focus of this laboratory has been to determine how ultraviolet radiation (UV) modulates the epidermal immune system. Low doses of UV-B administered to epidermal cells (EC) in vitro completely inhibited the ability of freshly-isolated Langerhans cells (fLC) to support the mitogenic response of T cells to anti-CD3 monoclonal antibodies (mAb). Exposure of fLC to low doses of UV-B in vitro prevented LC-T cell interactions and upregulation of ICAM-1 expression by fLC. Anti-ICAM-1 mAb inhibited the proliferative response of T cells to anti-CD3 mAb supported by fLC, confirming that the ICAM-l/LFA 1 interaction is critical in this system. LC that had been cultured for 24-72 h (cLC) were functionally resistant to UV-B and expressed increased levels of ICAM-1. Because cLC express several important adhesion molecules, the functional resistance of cLC to UV-B may not result from increased ICAM-1 expression alone. cLC were functionally resistant to UV-B even though UV-B was cytotoxic to cLC. This apparent paradox was resolved when it was discovered that anti-CD3 mAb-induced T cell activation became irreversible within several hours after culture initiation, before UV-B-- induced cytotoxicity became manifest. fLC caused T cells to become activated at a substantially slower rate. The enhanced accessory cell activity of cLC relative to fLC may be attributable to the fact that cLC express significant levels of several important adhesion molecules. UV-C and psoralen + UV-A had similar inhibitory effects on fLC function and ICAM-1 expression but markedly decreased LC survival in vitro. Re-examination of the effects of UV-B on LC survival revealed that although similar numbers of LC were recovered from cultures of irradiated and unirradiated EC 24 h after culture initiation, progressively fewer LC were recovered from cultures of irradiated EC at 48 and 72 h. These results indicate that low dose UV-B is lethal to LC in vitro and presumably also in vivo.
