Modulation of human t cell responses by nitric oxide and its derivative, s‐nitrosoglutathione

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Abstract
Objective. To examine the effects of nitric oxide (NO) and its more stable derivative, S-nitrosoglutathione (SNO-GSH), on the response of activated T lymphocytes. Methods. The effects of NO and SNO-GSH on DNA synthesis, interleukin-2 (IL-2) production, IL-2 receptor expression, and cGMP accumulation were determined in phytohemagglutinin–activated peripheral blood mononuclear cells (PBMC) and spleen T cells. Results. Nitric oxide (half-life [T1/2] < 15 seconds) did not inhibit T cell proliferation. However, the derivative SNO-GSH (25 μM) (T1/2 >2 hours) inhibited DNA synthesis by a mean ± SD of 65 ± 19.6% (P < 0.001) in PBMC and 75 ± 15% (P < 0.001) in spleen cells. Macrophage depletion of PBMC did not abrogate the inhibition. SNO-GSH had no effect on IL-2 production or IL-2 receptor expression. NO (25 μM) increased the cGMP content of PBMC (0.65 ± 0.15 pmoles/106 cells; P < 0.04), as did SNO-GSH (25 μM) in both PBMC (3.8 ± 1; P < 0.001) and spleen T cells (5.2 ± 1.2; P < 0.001). Methylene blue and hemoglobin, which are NO inhibitors, inhibited SNO-GSH–induced cGMP accumulation (P < 0.001). Conclusion. SNO-GSH inhibits T cell DNA synthesis independently of IL-2 production and in association with cGMP accumulation via a NO-dependent mechanism. We suggest that NO and its S-nitrosothiol derivatives may act as endogenous inhibitors of T cell–mediated inflammation.