Co-stimulation with LFA-1 triggers apoptosis in gamma delta T cells on T cell receptor engagement

Stimulation of T cells through the T cell receptor (TcR) initiate activation pathways, and paradoxically can also result in activation-induced cell death. Many factors influence a stimulated cell's decision to manifest one or the other. Here we show that co-stimulation with LFA-1 plays a key role in the choice between the two fates, differentiating between alpha beta and gamma delta T cells. Peripheral gamma delta. T cells but not alpha beta T cells undergo apoptosis upon co-cross-linking of TcR and LFA-1 in MRL lpr/lpr mice as well as +/+ mice. Our results suggest that apoptosis of gamma delta T cells is inducible by combined stimuli independent of the Fas-mediated pathway.