A. Beschin et al., TRYPANOSOMA-BRUCEI INFECTION ELICITS NITRIC OXIDE-DEPENDENT AND NITRIC OXIDE-INDEPENDENT SUPPRESSIVE MECHANISMS, Journal of leukocyte biology, 63(4), 1998, pp. 429-439
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.