Ultraviolet (UV) radiation induces in vivo a systemic immunosuppression with the generation of antigen-specific suppressor T cells. This UV effect may be important in modulating contact hypersensitivity (CHS) responses, viral and parasitic cell-mediated immunity, and may be critical in UV carcinogenesis, preventing the immune rejection of highly antigenic UV tumors. Recent studies have indicated that UV may modulate certain autoimmune diseases. The wavelengths of UV responsible for generating suppression (UVR, 250-320nm) do not penetrate the skin. An antigen presenting cell (APC) defect has been described in spleens of UV irradiated mice, and our recent studies indicated that, on a per cell basis purified dendritic cells (DC) from UV irradiated mice have decreased ability to present antigen. We propose to investigate the role of this APC defect in UV suppression. We will purify DC from lymph nodes of mice and investigate if UV alters either the number or the function of DC entering the draining lymph node in response to contact sensitiser on the skin. APC function will be assessed by in vitro primary and secondary proliferative responses, and by the ability to initiate CHS in vivo. We propose to investigate if the APC defect occurs in APC other than DC, and to investigate if it is associated with alterations to antigen uptake, processing, association between APC and T cells, or the production of accessory factors e.g. interleukin-1. Epidermal Langerhans cells (LC) alter on culture to a form resembling DC, becoming more efficient at initiating primary immune responses. We propose to test if irradiation with narrow bands of UV of different peak wavelengths alters either directly or systemically the ability of LC to progress to DC. Cultured LC from normal or UV mice will be assessed for surface markers, ultrastructural characteristics, and APC function in primary and secondary proliferative responses. We propose to test further a hypothesis derived from our previous studies that UV-induced suppression is initiated by an interaction between UV and a specific photoreceptor molecule in skin. We will administer the UV irradiated form of the photoreceptor (cis urocanic acid) and its naturally occurring counterpart (trans UCA) by specialized intradermal delivery systems, and establish if cis UCA can mimic the UV effects in CHS and on APC. We propose to confirm the observation that prior UV irradiation prevents experimental allergic encephalomyelitis, and auotimmune demyelinating disease of mice, and to investigate if altering timing, dose and wavelength of UV can generate suppressor T cells which can modulate the course of this disease.
