Transgenic expression of cyclin D1 in thymic epithelial precursors promotes epithelial and T cell development

We previously reported that precursors within the keratin (K) 8(+)5(+) thym ic epithelial cell (TEC) subset generate the major cortical K8(+)5(-) TEC p opulation in a process dependent on T lineage commitment. This report demon strates that expression of a cyclin D1 transgene in K8(+)5(+) TECs expands this subset and promotes TEC and thymocyte development. Cyclin D1 transgene expression is not sufficient to induce TEC differentiation in the absence of T lineage-committed thymocytes because TECs from both hCD3 epsilon trans genic and hCD3 epsilon/cyclin D1 double transgenic mice remain blocked at t he K8(+)5(+) maturation stage. However, enforced cyclin D1 expression does expand the developmental window during which K8(+)5(+) cells can differenti ate in response to normal hemopoietic precursors. Thus, enhancement of thym ic function may be achieved by manipulating the growth and/or survival of T EC precursors within the K8(+)5(+) subset.