The intestinal mucosal milieu comprises a variety of cell types and molecules including epithelial cells, leukocytes, stromal cells, endothelial cells, a neural network, extracellular matrix, cytokines growth factors and other molecules and cell types. Previous in vitro models of mucosal physiology and immunology have relied on monocultures of epithelial cells or leukocytes. It is the aim of this proposal to investigate the effect of co-culture of mucosal lymphocytes and epithelial cells at the levels of physiology, biochemistry, and molecular biology. Co-culture systems have already been developed in my sponsor's laboratory. In this proposal, experiments are designed to investigate the production of cytokines in response to co-culture, and their effect on the epithelial monolayer. The differential display polymerase chain reaction will also be utilized to identify genes whose transcription is newly modulated in response to co-culture. Lastly, a panel of monoclonal antibodies to such a co-culture system will be screened in order to identify differentially expressed epitopes, and their relevance to mucosal physiology. These experiments are anticipated to lead to enhanced understanding of the interaction between epithelial cells and intra-epithelial lymphocytes, and its contribution to inflammatory processes in the intestine. Thus, this proposal will test the hypothesis that intra-epithelial lymphocytes serve as an important regulator of intestinal epithelial cell function.