Strong TCR ligation without costimulation causes rapid onset of Fas-dependent apoptosis of naive murine CD4(+) T cells

Activation-induced cell death of T cells typically occurs late in the prima ry response after a prior proliferative response. Here, we describe a novel form of cell death in which purified naive murine CD4(+) cells undergo apo ptosis within 18 h in vitro after strong TCR ligation. Such rapid-onset TCR -mediated death of T cells does not involve cell division and is Fas-depend ent, inhibited by CD28 land IL-6) costimulation and enhanced by IL-4 and IL -7; by contrast, spontaneous death of CD4(+) cells cultured alone is Fas-in dependent and inhibited by IL-4 and IL-7. TCR-mediated Fas-dependent death of CD4(+) cells is prevented by combined TCR/Fas ligation and by drugs that inhibit calcineurin-dependent signaling and mitogen-activated protein kina se MEK1 activation.