TNF receptor-2-triggered apoptosis is associated with the down-regulation of Bcl-xL on activated T cells and can be prevented by CD28 costimulation.

Stimulation of recently activated T cells results in apoptosis of the responding cells, a process referred to as activation-induced cell death. This process is believed to play an important role in the regulation of immune homeostasis and is suggested to be mediated mainly by interactions between Fas and Fas ligand. Recent evidence indicates that TNF-alpha and TNFR2 interaction plays an important role in down-regulating activated T cells. The role of TNFR2 signaling in activation-induced cell death, however, has not been directly examined. We demonstrate here that 48-h activated T cells are most sensitive to TNFR2-induced apoptosis. Cross-linking of TNFR2 on activated T cells results in down-regulated protein and mRNA expression of Bcl-xL. Furthermore, CD28 costimulation can prevent anti-TNFR2-induced apoptosis and restore Bcl-xL expression. These results have potential implications for understanding the role of TNFR2 signaling in the regulation of T cell responses.