ABROGATION OF EPIDERMAL ANTIGEN-PRESENTING CELL FUNCTION BY ULTRAVIOLET RADIATION ADMINISTERED IN VIVO

Abstract

The exposure of animals [mice] to UV radiation (UVR) can result in dramatic alterations to their immunologic potential. Loss of ability to be contact-sensitized to skin-reactive chemicals applied to UVR-exposed surfaces, and an enhanced susceptibility to tumors induced by UVR represent 2 well-documented effects of such exposure. The skin Langerhan''s cell (LC) is a cell type, having antigen presentation capabilities, which is functionally inactivated by UVR. The localized loss in the ability to induce a contact hypersensitivity (CS) response and the early events associated with the acquisition of a tumor-susceptible state have been hypothesized to involve LC inactivation by UVR. The relationship between the UVR-mediated loss of CS responsiveness and antigen-presenting cell (APC) function by LC following in vivo exposure of animals to UVR. The UVR-mediated loss of CS responsiveness was both time-dependent and dosage-dependent, but the loss of epidermal APC function following the UVR exposure of dissociated epidermal cells or skin was immediate and dosage-dependent. The lack of time dependency associated with the loss of epidermal APC function may be due to the nature of the assay system being employed. Add-back experiments, using the proliferation of purified antigen-primed T cells as a read-out system to evaluate APC function, require that the accessory cell be totally functional. Initiation of CS responses may still be possible with LC that are partially UVR-inactivated. Lymph node-associated and circulating accessory cells could be integrated into the response, providing any necessary components that the UV-inactivated LC lacks. This possibility was tested and from these studies it was concluded that this is indeed a viable possibility. The results provide a possible explanation for apparent differences in LC UVR susceptibility observed when in vitro and in vivo assays are employed.