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 document ed 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 monocy togenes-immune mice produced IFN-gamma upon stimulation with specific antigen and NO was generated in culture. When N-G-monomethyl-L-arginin e (NMMA) was added to the culture at a dose sufficient for the complet e blockade of NO production, there was a significant level of enhancem ent of IFN-gamma production, which was also dose dependently correlate d 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 cult ure with NMMA. The endogenously produced NO suppressed T-cell prolifer ation which can be restored by the addition of NMMA. Sodium nitropruss ide, a spontaneous NO generator, inhibited T-cell proliferation dose d ependently and suppressed IFN-gamma production. Taken together, it may be concluded that NO down-regulates IFN-gamma production mainly by in hibiting T-cell proliferation. (C) 1996 Academic Press, Inc.