AUTOCRINE NITRIC-OXIDE MODULATES CD95-INDUCED APOPTOSIS IN GAMMA-DELTA T-LYMPHOCYTES

gamma delta T lymphocytes play an important early role in the defense against pathogens. Their function is terminated by acquisition of susc eptibility to CD95-triggered apoptosis. Here we show that the regulati on of this process depends on the activity of the endothelial NO synth ase expressed by gamma delta T lymphocytes, which is modulated in an a ctivation-dependent way. The effects of nitric oxide thus generated, m ediated via cGMP generation, are exerted at at least two sites along t he CD95 signaling cascade: one at, or upstream, and the other downstre am of ceramide generation. At either site, nitric oxide/cGMP action is sufficient for protection from apoptosis. The effect of NO is selecti ve for apoptosis induced by CD95 cross-linking, since it does not affe ct apoptotic program triggered by other stimuli. The evidence here rep orted demonstrates a new physiological role for nitric oxide, acting a s a survival factor for T lymphocytes.