Activation of Cdk2 is a requirement for antigen-mediated thymic negative selection

Apoptosis plays a critical role in T cell development and thymic selection. Thymocytes which undergo antigen-induced negative selection have been demo nstrated to die by apoptosis. Despite this, relatively little is known abou t the specific apoptotic pathway involved in negative selection. We have ex amined the role of cyclin-dependent kinase 2 (Cdk2), a key regulator of thy mocyte apoptosis, in this process. Stimulation of thymocytes with cognate a ntigen leads to a large increase in Cdk2 kinase activity. We also show that pharmacological inhibitors of Cdk2 block thymocyte apoptosis in response t o antigen. Our data show that Cdk2 activity is essential for the apoptotic pathway used in negative selection.