Nitric-Oxide Mediates Suppression of T-Cell Responses in Murine Trypanosoma-Brucei Infection

African trypanosomes induce a generalized state of immunosuppression in their mammalian hosts. One characteristic of this is a suppression of lymphocyte responses to mitogen, which is mediated by suppressor macrophages. We investigated the involvement of nitric oxide in this phenomenon. Both peritoneal and splenic cell cultures from infected mice released nitrite and this was inhibitable by N(G)-monomethyl L-arginine (L-NMMA). The release of nitrite correlated with suppressed splenic Tcell proliferative responses to concanavalin A. It was shown that adherent spleen cells from infected mice mediate suppression, which could be abrogated by L-NMMA. These results suggest that in T brucei infection, the activation of macrophages to produce nitric oxide leads to impaired lymphocyte responses and immunosuppression.