The objective of these studies is to identify and characterize a specialized set of epidermal and splenic ultraviolet radiation (UVR)-resistant, I-J bearing, antigen-presenting cells necessary for the generation of suppressor T cells in mice. The discovery of these cells has important implications for the understanding of immunity in the skin and the local effects of UVR exposure on antigen processing. Furthermore, these cells may play a role in the development of UVR-induced skin cancers. The activity of these cells in the generation of suppressor T cells specific for UVR-induced tumors in animals chronically exposed to UVR and also in a hapten specific system will be defined. The sensitivity of the generation of these tumor specific suppressor cells to agents such as anti-I-J monoclonal antibodies, cyclophosphamide, psoralen plus UVA therapy (PUVA), and various chemotherapeutic agents will be examined in functional assays. Detailed characterization of the phenotype of these I-J+ antigen-presenting cells (APC) involved in the generation of supressor cell activity will be performed. Such characerization will include detailed Ia phenotyping, the search for Fc receptors, theta antigen, surface immunoglobulin, and C3 receptors of these special APC. The ability of these cells to phagocytose ferritin, the sensitivity of these cells to UVR, and a determination of the cells' buoyant density will also be evaluated. These phenotypic and functional parameters can then be compared to other well-characterized types of APC. Other studies will be undertaken to determine if these cells originate in the bone marrow and to what anatomic sites they migrate. In particular, we will determine if special bone marrow derived APC involved in suppressor cell activation migrate to the skin where they play a critical role in modulating inflammatory responses and also might contribute to skin neoplasia. Finally, because interleukin 1 (IL-1), an important signal in helper T cell activation, has been demonstrated to partially correct UVR-inducted defects in 1-A bearing APC function in vitro and in vivo, we will attempt to modulate the response of the UVR treated host to UVR-induced regressor tumors in vivo by administration of IL-1 and other lymphokines.
| Granstein, R D (1990) Photoimmunology. Semin Dermatol 9:16-24 |
| Margolis, R J; Sherwood, M; Maytum, D J et al. (1989) Longwave ultraviolet radiation (UVA, 320-400 nm)-induced tan protects human skin against further UVA injury. J Invest Dermatol 93:713-8 |
