Evidence for an Intermediate Between the Immune System and Ultraviolet Light in the Skin of Mice Undergoing Ultraviolet Carcinogenesis

Abstract

Tumors induced by ultraviolet (UV) irradiation in mice are highly antigenic and are immunologically rejected by normal syngeneic mice. Periodic UV irradiation of normal mice renders them incapable of making an immune response against these tumors. It seems reasonable to postulate that UV irradiation induces an intermediate in the skin of mice which might be responsible for the immune unresponsiveness to UV-induced tumors. To demonstrate the existence and location of this putative intermediate, skin grafts, skin extracts, and plasma were tested for either tolerogenic or immunogenic activity. Mice that received whole-body grafts of UV-irradiated skin were more susceptible to challenge with UV-induced tumors than mice which received grafts of unirradiated skin. This increased susceptibility to challenge was not detected with a chemically-induced syngeneic tumor. Smaller areas of skin were unable to tolerize or immunize normal recipients. Saline extracts of UV-irradiated skin possessed immunogenic activity in the particulate fraction, but no tolerogenic activity was found in the soluble fraction. Plasma from UV-irradiated donors was not able to immunize normal recipients to UV-induced tumors but was able to suppress the anti-tumor response. These results suggest that an intermediate is produced in the skin of UV-irradiated mice which might be responsible for the initial step in rendering UV-irradiated mice immunologically unresponsive to UV-induced tumors.