NITRIC-OXIDE PRODUCTION BY SPLENIC MACROPHAGES IS NOT RESPONSIBLE FORT-CELL SUPPRESSION DURING ACUTE INFECTION WITH LACTATE DEHYDROGENASE-ELEVATING VIRUS

Cellular immune responses of mice are transiently suppressed during ac ute infection with lactate dehydrogenase-elevating virus (LDV). Immuno suppression of mice correlated with a greatly impaired in vitro prolif erative response of the majority of the T cells to Con A or anti-CD3 A bs, which could not be reversed by the addition of rIL-2. We have exam ined whether the T cell suppression is caused by nitric oxide (NO) pro duced by activated macrophages, which are observed in acutely infected mice. Spleen macrophages from 3-day LDV-infected mice exhibited a 6- to 10-fold increased potential for producing NO, measured as nitrite o r nitrite plus nitrate in the culture fluid, but produced significant amounts of NO in vitro only when incubated with IFN-gamma produced by Con A-stimulated T cells in the spleen cell population. Furthermore, w e found that the concentrations of NO produced by macrophages in cultu res of spleen cells from LDV-infected mice in the presence of IFN-gamm a were insufficient to cause a reduction in the proliferative response of T cells in the spleen cell population. An excess of activated macr ophages had to be added to achieve T cell suppression. NO inhibition o f Con A-induced T cell proliferation exhibited a very sharp dose-respo nse curve. In one experiment little suppression was observed at NO con centrations equivalent to 12 mu M nitrite and below, whereas almost co mplete inhibition was observed at twice the NO concentration. We concl ude that NO is not responsible for T cell suppression in LDV-infected mice.