INTRACELLULAR SIGNALING EVENTS DURING POSITIVE AND NEGATIVE SELECTIONOF CD4(-VITRO()CD8(+) THYMOCYTES IN)

We have used in vitro models of thymocyte positive and negative select ion in conjunction with selective inhibitors of the TCR-mediated signa ling cascade to investigate the intracellular signaling events that me diate these processes. We report that Ro 31.8425, a potent and selecti ve inhibitor of protein kinase C, which blocks the activation selectio n of CD4(+)8(+) of mature T cells in a dose-dependent fashion, has no effect on either positive or negative thymocytes. in contrast, cyclosp orin A fails to prevent negative selection, but inhibits positive sele ction through a direct effect on developing thymocytes, rather than th rough the perturbation of stromal cell support. Thus, our data suggest that positive and negative selection may operate via distinct intrace llular signaling pathways. The journal of Immunology, 1995, 154: 3636- 3643.