VIRAL SUPERANTIGEN-INDUCED NEGATIVE SELECTION OF TCR TRANSGENIC CD4(+) CD8(+) THYMOCYTES DEPENDS ON ACTIVATION, BUT NOT PROLIFERATION

T-cell negative selection, a process by which intrathymic immunologica l tolerance is induced, involves the apoptosis-mediated clonal deletio n of potentially autoreactive T cells. Although different experimental approaches suggest that this process is triggered as the result of ac tivation-mediated cell death, the signal transduction pathways underly ing this process is not fully understood. In the present report we hav e used an in vitro system to analyze the cell activation and prolifera tion requirements for the deletion of viral superantigen (SAg)-reactiv e V(beta)8.1 T-cell receptor (TCR) transgenic (TG) thymocytes. Our res ults indicate that in vitro negative selection of viral SAg-reactive C D4(+) CD8(+) thymocytes is dependent on thymocyte activation but does not require the proliferation of the negatively signaled thymocytes. ( C) 1998 by The American Society of Hematology.