The major focus of this laboratory has been to determine how ultraviolet B (UV-B) radiation modulates the epidermal immune system. We have found that low doses of UV-B radiation administered to epidermal cells (EC) in vitro completely inhibit the ability of freshly isolated Langerhans cells (fLC) to support the mitogenic response of T cells to anti CD3 antibodies. This inhibitory effect appears to result from the direct action of UV-B on LC and is not due to cytotoxicity. LC that have been cultured for 24-72 hours (cLC) become progressively more resistant to UV-B radiation, an observation which correlates with the progressive increase in the expression of the intercellular adhesion molecule ICAM-1 by cLC. We have found that anti-murine ICAM-1 antibodies inhibit the proliferative response of T cells to anti CD3 antibodies supported by fLC or cLC, confirming that the ICAM-1/LFA-1 interaction is critical in this system. We have also found that exposure of fLC to low doses of UV-B radiation in vitro prevents them from expressing increased levels of ICAM-1 after a 24 hours culture period. Finally, irradiated fLC do not form clusters with T cells in response to anti CD3 suggesting that ICAM-1 is functionally deficient as well. We are also studying the effect of UV-B radiation on protein antigen processing in a model system where expression of costimulatory molecules (eg. ICAM-1) is unimportant. In collaborative studies, we are examining the accessory cell activity of EC from essential fatty acid (EFA) deficient mice. EC from EFA deficient mice are better stimulators of T cell responses to protein antigens and alloantigens than EC from normal mice. LC number and class II antigen expression by LC is unaltered in EFA deficient mice, as is cytokine production. The most striking difference between EC from EFA deficient and normal mice is that some EFA deficient keratinocytes (KC) express high levels of class II antigens, We have suggested that EFA deficient KC serve as """"""""costimulators"""""""" of LC dependent T cell responses.
