A critical role for Fas ligand in the active suppression of systemic immune responses by ultraviolet radiation

Induction of antigen-specific suppression elicited by environmental insults , such as ultraviolet (UV)-B radiation in sunlight, can inhibit an effectiv e immune response in vivo and may contribute to the outgrowth of UV-induced skin cancer. Although W-induced DNA damage is known to be an initiating ev ent in the immune suppression of most antigen responses, the underlying mec hanism(s) of such suppression remain undefined. In this report, we document that Fas ligand (FasL) is critical for W-induced systemic immune suppressi on. Normal mice acutely exposed to UV exhibit a profound suppression of bot h contact hypersensitivity and delayed type hypersensitivity (DTH) reaction s and the development of transferable antigen-specific suppressor cells. Fa sL-deficient mice exposed to UV lack both transferable suppressor cell acti vity and primary suppression to all antigens tested, with the exception of the DTH response to allogeneic spleen cells. Interestingly, suppression of this response is also known to occur independently of UV-induced DNA damage . Delivery of alloantigen as protein, rather than intact cells, restored th e requirement for Fast in UV-induced immune suppression of this response. T hese results substantiate that FasL/Fas interactions are essential for syst emic W-induced suppression of immune responses that involve host antigen pr esentation and suggest an interrelationship between UV-induced DNA damage a nd Fast in this phenomenon. Collectively, our results suggest a model where by UV-induced DNA damage disarms the immune system in a manner similar to t hat observed in immunologically privileged sites.