Trypanosoma brucei infection elicits nitric oxide-dependent and nitric oxide-independent suppressive mechanisms.

During murine Trypanosoma brucei in- fection, macrophages contribute significantly to the inhibition of T cell responses. Although nitric oxide (NO) was shown to play a central role in macrophage-mediated splenic suppression, macro- phage-mediated lymph node suppression occurred in an interferon-g (IFN-g)-dependent manner. In this study, using NO inhibitor N G -monomethyl-L- arginine and anti-IFN-g antibodies, the relative contribution of NO and IFN-g to the active inhibi- tion of ex vivo concanavalin A-induced T cell proliferation taking place in the spleen and the lymph nodes of T. brucei-infected mice was investi- gated. NO contributes to the suppressive activity of spleen and lymph node cells only during early-stage infection. The existence of NO-independent sup- pressive pathway was further evidenced in IFN-g -/- - infected mice. Spleen cells from such animals do not produce NO but exert significant suppressive activity during the whole course of infection. In contrast in the lymph nodes, no suppressive activity is recorded at any moment of infection. Moreover, addition of exogenous IFN-g to cultures containing lymph node cells from IFN-g -/- -infected mice does not impair proliferation despite NO production in such cultures. Thus during late-stage infection, an IFN-g-independent suppressive mechanism is elic- ited in the spleen, whereas in the lymph nodes, IFN-g is required yet not sufficient to inhibit T cell proliferation. J. Leukoc. Biol. 63: 429-439; 1998.