Thymocytes and thymic epithelial cells (TECs) relay mutually inductive signals that are required for the development of both cell types. One important aspect of thymic cross-talk is the production of IL-7 by TECs. IL-7 is a pleiotrophic and nonredundant cytokine that is essential for thymocyte development. We have used in situ hybridization (ISH) analysis to show that IL-7 is expressed in the third pharyngeal pouch endoderm by embryonic day 11.5 during thymic organogenesis. Interestingly, IL-7 expression is restricted to the thymic fated domain of the early thymus/parathyroid common primordium. Therefore, we propose that IL-7 expression can be exploited to genetically mark fetal progenitors that are developmentally destined to generate the TEC compartment. A primary goal of this proposal is to produce novel transgenic strains in which the IL-7 promoter drives a Cre recombinase transgene or a human CD25 reporter gene. These transgenic mice will provide experimental models for future experiments designed to trace the origin and lineage relationships among phenotypically diverse TEC subsets. In conjunction with the plan to label IL-7 expressing epithelial precursors, we propose to identify the mature epithelial subsets and non-epithelial cells that produce IL-7 in the thymus. Although the basic and clinical significance of IL-7 in regulating T cell development is well established, there is surprisingly little information on the specific cell types that produce IL-7 in the thymus. For example, it has not been established whether nonepithelial thymic stromal cells (e.g. endothelial cells and dendritic cells) express IL-7. This information is vital for future studies that focus on promoting or restoring IL-7 expression in the thymus of aged or immune compromised individuals. Therefore, the second major goal of this proposal is to identify and localize IL-7 producing cells in the thymus of young and aged mice.
