Nitric oxide‐mediated inhibition of caspase‐dependent T lymphocyte proliferation

Nitric oxide (NO), a pleiotropic signaling molecule produced at sites of inflammaion, is a powerful inhibitor of lymphocyte proliferation. Caspases, central effector proteases in apoptosis, have recently been implicated as critical mediators of T cell activation. We and others have shown that NO can inhibit caspases by S‐nitrosylation, which is reversible by the reducing agent dithiothreitol (DTT). The purpose of the present study was to determine whether NO inhibits lymphocyte proliferation by modulating caspase activity. Caspase inhibition with z‐VAD‐fmk blocked T cell proliferation. NO‐dependent inhibition of T cell proliferation was associated with an inhibition of caspase activity and activation, and this effect was reversible by DTT. Previous studies demonstrated inhibition of apoptosis through S‐nitrosylation of caspases; the present studies extend this effect to inhibition of caspase‐dependent T cell proliferation.

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