NITRIC-OXIDE MODULATES INTERLEUKIN-2-INDUCED PROLIFERATION IN CTLL-2 CELLS

RIE role of the L-arginine-nitric oxide metabolic pathway was explored for interleukin-2-induced proliferation in the cytotoxic T lymphocyte clone CTLL-2. Specific inhibition of nitric oxide synthase significan tly diminished, in a concentration-dependent manner, H-3-thymidine upt ake of CTLL-2 cells in response to different concentrations of interle ukin 2. Withdrawal of L-arginine from culture medium resulted as poten t as the higher inhibition obtained when blocking nitric oxide synthas e with L-arginine analogues. Furthermore, intermedial concentrations o f L-arginine and exogenous nitric oxide donors were found for achievin g optimal IL-2 induced proliferation of CTLL-2. These findings prompte d us to suggest that intra- and/or inter-cellular nitric oxide signall ing may contribute to the medulation of the IL2 mitogenic effect upon cytotoxic T lymphocytes.