THYMIC CORTICAL EPITHELIUM IS SUFFICIENT FOR THE DEVELOPMENT OF MATURE T-CELLS IN RELB-DEFICIENT MICE

Thymic development of T lymphocytes progresses as a consequence of bot h TCR-mediated and non-TCR-mediated interactions between thymocytes an d stromal cells. As relB-deficient mice appear to lack thymic medullar y epithelium and mature dendritic cells, we studied the effect of this ''cortex-only'' thymus on T cell development. Two major consequences were observed. First, in both relB mutant and TCR transgenic/relB muta nt mice, positive selection of both TCR alpha beta and gamma delta T c ells appeared to proceed normally, with export of fully functional T c ells to the periphery, suggesting that the thymic medullary stromal ce lls are not required for full maturation of T cells nor is an organize d medullary compartment required for accumulation of mature single pos itive CD4 and CD8 T cells. Second, thymic negative selection was impai red, as evidenced by significant autoreactive proliferative responses to normal spleen stimulators. Peripheral T cells in relB mutant mice s howed an unusually high proportion of CD69(+) and CD44(high) cells. Wh ile some of these cells may be autoreactive T cells, most of the cells appeared to be activated by cytokines produced by relB mutant nonlymp hoid cells, as the effect is minimized in relB mutant bone marrow chim eras. In sum, while the TCR-mediated steps in T cell maturation requir e both thymic cortex and medulla (epithelium and dendritic cells) for normal positive and negative selection of the repertoire, non-TCR-medi ated interactions in the thymic cortex alone are sufficient to generat e mature functional T cells.