Suppression of IFN-γ Production fromListeria monocytogenes-Specific T Cells by Endogenously Produced Nitric Oxide

The induction of nitric oxide (NO) by IFN-γ 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-γ production. In the present study, CD4+T cells fromListeria monocytogenes-immune mice produced IFN-γ upon stimulation with specific antigen and NO was generated in culture. WhenNG-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-γ production, which was also dose dependently correlated with addition of NMMA. RT-PCR revealed that IFN-γ 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-γ production. Taken together, it may be concluded that NO down-regulates IFN-γ production mainly by inhibiting T-cell proliferation.