Bad can act as a key regulator of T cell apoptosis and T cell development

Bad is a distant relative of Bcl-2 and acts to promote cell death. Here, we show that Bad expression levels are greatly increased in thymocytes during apoptosis. We generated ban transgenic mice to study the action of upregul ated Bad expression on T cell apoptosis. The T cells from these mice are hi ghly sensitive to apoptotic stimuli, including anti-CD95. The numbers of T cells are greatly depleted and the processes of T cell development and sele ction are perturbed. We show that the proapoptotic function of Bad in prima ry T cells is regulated by Akt kinase and that Bad overexpression enhances both cell cycle progression and interleukin 2 production after T cell activ ation. These data suggest that Bad can act as a key regulator of T cell apo ptosis and that this is a consequence of its upregulation after exposure to death stimuli.