TRYPANOSOMA-BRUCEI INFECTION ELICITS NITRIC OXIDE-DEPENDENT AND NITRIC OXIDE-INDEPENDENT SUPPRESSIVE MECHANISMS

During murine Trypanosoma brucei infection, macrophages contribute sig nificantly to the inhibition of T cell responses, Although nitric oxid e (NO) was shown to play a central role in macrophage-mediated splenic suppression, macrophage-mediated lymph node suppression occurred in a n interferon-gamma (IFN-gamma)-dependent manner, In this study, using NO inhibitor N-G-monomethyl-L-arginine and anti-IFN-gamma antibodies, the relative contribution of NO and IFN-gamma to the active inhibition of ex vivo concanavalin A-induced T cell proliferation taking place i n the spleen and the lymph nodes of T, brucei-infected mice was invest igated, NO contributes to the suppressive activity of spleen and lymph node cells only during early-stage infection, The existence of NO-ind ependent suppressive pathway was further evidenced in IFN-gamma(-/-)-i nfected mice, Spleen cells from such animals do not produce NO but exe rt significant suppressive activity during the whole course of infecti on, In contrast in the lymph nodes, no suppressive activity is recorde d at any moment of infection, Moreover, addition of exogenous IFN-gamm a to cultures containing lymph node cells from IFN-gamma(-/-)-infected mice does not impair proliferation despite NO production in such cult ures, Thus during late-stage infection, an IFN-gamma-independent suppr essive mechanism is elicited in the spleen, whereas in the lymph nodes , IFN-gamma is required yet not sufficient to inhibit T cell prolifera tion.