A THYMIC EPITHELIAL-CELL LINE INDUCES BOTH POSITIVE AND NEGATIVE SELECTION IN THE THYMUS

TCR engagement in the thymus results in both survival and elimination signals for developing thymocytes. To examine whether both signals can be provided by the same cell type, we investigated the ability of a t hymic epithelial cell (TEC) line 427:1, previously shown to allow posi tive selection in the thymus, to induce clonal deletion of immature th ymocytes. [H-2b/s-->H-2s] bone marrow chimeras are non-responsive to a ntigens in the context of H-2b. However, chimeras that underwent intra thymic injection of H-2b/s 427.1 cells expressing vesicular stomatitis virus (VSV) nucleocapsid antigen acquired the ability to raise influe nza, but not VSV specific H-2b restricted cytotoxic T lymphocyte (CTL) responses. The ability of 427.1 cells to delete CD4+CD8+ thymocytes w as determined using mice transgenic for the TCR specific for ovalbumin (OVA) in the context of H-2K(b). OVA transfected, but not mock transf ected 427.1 TECs, induced in vitro deletion of CD4+CD8+ TCR transgenic thymocytes manifested as a down-modulation of CD4 and CD8 molecules, a shift in the side versus forward scatter characteristics of thymocyt es, and appearance of thymocytes with subdiploid content of DNA indica ted the ongoing process of DNA fragmentation. The finding that the sam e TEC line is capable of inducing both positive and negative selection in the thymus suggests that thymocytes bearing TCRs specific for self peptides expressed by positively selecting thymic epithelium can be d eleted. Therefore the expression of a unique set of MHC associated pep tides by TECs does not appear to be the basis for the positive outcome of the TCR ligation on immature thymocytes.