SUSCEPTIBILITY AND RESISTANCE TO ANTIGEN-INDUCED APOPTOSIS IN THE THYMUS OF TRANSGENIC MICE

Injection of TCR transgenic mice with antigenic peptide results in the deletion of immature thymocytes expressing the transgenic TCR, We hav e analyzed this process in mice transgenic fbr a TCR (F5) that recogni zes a peptide from the influenza nucleoprotein (NP68), To determine wh ether deletion of immature thymocytes is the result of specific recogn ition of the antigenic peptide by the thymocytes or mature T cell acti vation, bone marrow chimeric :mice were generated using a mixture of c ells from F5 transgenic and nontransgenic mice. Injection of these mic e with antigenic peptide leads to the preferential depletion of F5 tra nsgenic thymocytes, whereas nontransgenic thymocytes remain largely un affected. Furthermore, exposure of F5 fetal thymic lobes to peptide le ads to thymocyte deletion even though no mature single positive T cell s are present at this stage. These data suggest that Ag-induced death of immature thymocytes is due to peptide-specific recognition, althoug h activated mature T cells appear to potentiate such deletion. Further administration of antigenic peptide to F5 mice results in the appeara nce of double-positive thymocytes that are resistant to Ag or anti-CD3 -induced apoptosis. These data suggest a change in the ability of the cells to signal through the TCR-CD3 complex, resembling the state of a nergy induced in peripheral T cells following chronic exposure to Ag.