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

Eur J Immunol. 1996 Mar;26(3):539-43. doi: 10.1002/eji.1830260306.


African trypanosome infections result in lymphocyte unresponsiveness and anemia in the mammalian host. In murine infections, these effects are 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 lysates 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 exposed 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-infected mice, suggesting that a combination of trypanosome-released macrophage-activating factors and IFN-gamma are a trigger of immune dysfunction in trypanosomiasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Drug Synergism
  • Enzyme Induction / drug effects
  • Enzyme Induction / immunology
  • Female
  • Immune Tolerance / drug effects
  • Interferon-gamma / pharmacology*
  • Interferon-gamma / physiology
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred C3H
  • Nitric Oxide / pharmacology*
  • Nitric Oxide Synthase / biosynthesis*
  • Protozoan Proteins / pharmacology*
  • Solubility
  • Spleen / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / enzymology*
  • Trypanosoma brucei brucei / immunology*
  • Trypanosoma brucei brucei / physiology
  • Trypanosomiasis, African / enzymology
  • Trypanosomiasis, African / immunology*


  • Protozoan Proteins
  • Nitric Oxide
  • Interferon-gamma
  • Nitric Oxide Synthase