The objective of these studies is to characterize a specialized set of epidermal and splenic ultraviolet radiation (UVR)-resistant antigen-presenting cells (APC) that induce the generation of suppressor T (Ts) 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. These cells may play a role in the development of UVR-induced skin tumors by presenting tumor-associated antigens (TAA) for activation of tumor-specific Ts cells that occur in chronically UVR treated mice. Progress to date has demonstrated that those epidermal cells (EC) that induce Ts cells are high-density (HD), glass-adherent (adhHD-EC), I-A+ and Thy 1- phenotypically, and I-J restricted, cyclophosphamide (CY)-sensitive, and UVR-resistant functionally. Ts cells induced by iv administration of hapten-coupled HD-EC differ from those induced by iv administration of hapten-coupled spleen cells in that they inhibit both afferent and efferent phases of the immune response in an antigenically non-specific manner; thus they are similar to what have been termed third-order Ts cells. Further analyses of EC that activate Ts cells will include examination for Fc and C3 receptors, surface immunoglobulin, and phagocytic activity. The ability of these cells to present TAA for suppression will be examined. Other studies will determine if these cells are bone marrow-derived and to what anatomic sites they migrate. adhHD-EC lose their ability to induce suppresion after 3 days in culture. The ability of certain cytokines to prevent this loss of activity in culture will be examined. We will also attempt to produce a hybridoma line from EC with activity to prime for suppression. The development of such a line would allow for more precise determination of the biological activities of these cells and their trafficking patterns in vivo. Other work has demonstrated that similar cells, capable of activating Ts cells, are present in the anterior portion of the murine eye. This finding may explain, in part, the immunologic privilege of the anterior chamber. Characterization of these cells will be initiated. Administration of anti-I-J antibody or CY to mice during chronic UVR exposure prevents the generation of UVR- regressor tumor Ts cells. Utilizing the ABA hapten-system, we will examine at what locus this inhibition occurs. Understanding how these agents work may be useful for designing novel approaches to modify tumor behavior in vivo.
| 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 |
