Specialized ability of thymic epithelial cells to mediate positive selection does not require expression of the steroidogenic enzyme P450scc

Thymic epithelial cells are uniquely efficient in mediating positive select ion, suggesting that in addition to providing peptide/MHC complexes for TCR ligation, they may also provide additional support for this process. Recen t studies have shown that although engagement of either the TCR or glucocor ticoid (GC) receptors can individually induce apoptosis in thymocytes, toge ther these signals are mutually antagonistic. This had led to the suggestio n that local GC production by thymic epithelial cells, by opposing TCR sign aling for apoptosis, provides the basis of the ability of these cells to me diate thymocyte positive selection. In this paper we have examined this pos sibility directly and shown that highly purified cortical epithelial cells, which have the functional ability to mediate positive selection in reaggre gate cultures, do not express mRNA for the key steroidogenic enzyme P405scc , Thus we conclude that the ability of thymic epithelial cells to support p ositive selection does not rely on their ability to produce GC. However, we find that P450scc mRNA is up-regulated in thymocytes on the initiation of positive selection, raising the possibility that any local protective effec t of steroid production is mediated at the level of thymocytes themselves.