Suppression of IFN-gamma production from Listeria monocytogenes-specific T cells by endogenously produced nitric oxide

The induction of nitric oxide (NO) by IFN-gamma has been well documented in a variety of experimental settings, but so far there has been no report on whether the endogenously produced NO can suppress IFN-gamma production. In the present study, CD4+ T cells from Listeria monocytogenes-immune mice produced IFN-gamma upon stimulation with specific antigen and NO was generated in culture. When NG-monomethyl-L-arginine (NMMA) was added to the culture at a dose sufficient for the complete blockade of NO production, there was a significant level of enhancement of IFN-gamma production, which was also dose dependently correlated with addition of NMMA. RT-PCR revealed that IFN-gamma mRNA per given amount of total RNA remained the same irrespective of NO blockade by NMMA; however, total RNA recovery was significantly higher in the culture with NMMA. The endogenously produced NO suppressed T-cell proliferation which can be restored by the addition of NMMA. Sodium nitroprusside, a spontaneous NO generator, inhibited T-cell proliferation dose dependently and suppressed IFN-gamma production. Taken together, it may be concluded that NO down-regulates IFN-gamma production mainly by inhibiting T-cell proliferation.