MECHANISMS OF UV-INDUCED IMMUNE SUPPRESSION

皮肤暴露于紫外线（UV）辐射抑制T细胞

Epicutaneous exposer to ultraviolet (UV) radiation suppresses T cell- mediated immune responses to antigens encountered in the skin and permits the growth of highly immunogenic skin cancers in laboratory animals. Immune suppression by UV radiation is mediated by multiple, complex, and interacting mechanisms. Recent studies indicate the suppression is triggered by DNA damage followed by production of immunosuppressive cytokines, loss of antigen presenting cells (APC) from the skin, alteration of the functions of remaining APC, and induction of antigen-specific suppressor T cells. However, the regulation nd interaction of these APC, and induction of antigen-specific suppressor T cells. However, the regulation and interaction of these APC and cytokine pathways are unclear and appears to be different for contact hypersensitivity (CHS) reactions to allergens in skin and delayed type hypersensitivity (DTH) reactions to microorganisms. We have recently shown that crude extracts of Aloe barbadensis gel protects CHS and DTH responses against suppression by UV radiation. Because Aloe extract provides broad protection for immune responses that are abrogated by UN by different mechanisms, it may act as a central controlling point in suppression. Alternatively Aloe may contain several agents that act on CHS and DTH separately. Furthermore, Aloe is chemically distinct from antibodies, cytokines, or other agents that have been used to probe suppression pathway induced by UV radiation, and it may be acting by a novel mechanism(s). We will test these hypotheses by exposing mice to UV radiation and examining the effect of Aloe treatment on the production of the regulatory cytokines TNF-alpha, IL-10, and Il-12 in cultured keratinocyte cell liens and in skin. We will investigate whether protection of CHS and DTH responses is mediated separately by different components in Aloe. We will also examine the effect of Aloe on the function of APC from the draining lymph nodes using the murine model of CHS response to the hapten fluorescein isothiocyanate, and the DTH response to Candida albicans. In addition, we propose to investigate the ability of Aloe to preserve immunity to UV-induced skin cancers. Clarification of the relationship of the CHS and DTH models to cutaneous tumor immunity may permit the design of therapeutic agents that are more effective in protecting humans against the development of skin cancer.