NITRIC OXIDE-MEDIATED SUPPRESSION OF T-CELL RESPONSES DURING TRYPANOSOMA-BRUCEI INFECTION - SOLUBLE TRYPANOSOME PRODUCTS AND INTERFERON-GAMMA ARE SYNERGISTIC INDUCERS OF NITRIC-OXIDE SYNTHASE

African trypanosome infections result in lymphocyte unresponsiveness a nd anemia in the mammalian host. In murine infections, these effects a re mediated by suppressor macrophages releasing nitric oxide (NO). We investigated the mechanism of activation of macrophages to produce NO during trypanosomiasis in vitro. A soluble component of trypanosome ly sates induced NO synthesis in peritoneal macrophage cultures only when the macrophages were co-stimulated with interferon-gamma (IFN-gamma). The macrophage-activating factor was also released in a soluble form by live bloodstream-form trypanosomes, but not procyclic trypanosomes. When splenocyte cultures were expected to IFN-gamma and trypanosomes, an NO-dependent suppression of T cell proliferation occurred. This is similar to the suppression observed in the spleens of trypanosome-inf ected mice, suggesting that a combination of trypanosome-released macr ophage-activating factors and IFN-gamma are a trigger of immune dysfun ction in trypanosomiasis.