Interference in general immune function by parasite infections; African trypanosomiasis as a model system

Many parasitic diseases are accompanied by an immunosuppression which may affect only parasite-specific responses in some infections or lead to a general dysfunction of the immune system in others. African trypanosomiasis causes a particularly severe disorder of the immune system and this serves as a model system for analysis of the cellular basis of a parasite-induced general immune dysfunction affecting nearly all T- or B-lymphoid cell subpopulations. The nature of the parasite products causing havoc in the immune system may well vary in different infections and still remains to be defined. Trypanosome membrane fractions are active in vitro or in vivo but we have no evidence for a direct action on B- or T-cells. In vitro, both in man and mouse, T-cells are stimulated, but only in the presence of accessory cells. This points to the importance of host-derived immunosuppressive factors in the immune dysfunction. We have evidence that macrophages, after uptake of parasites in the presence of antibodies, are at least one target cell for parasite action. They can mediate immunosuppression and undergo changes in phenotype and mediator release during the course of infection. The macrophages show all the characteristic signs of activation, which can also be induced by other means and other infective agents such as BCG. Thus, macrophage activation would provide a common pathway for induction of a general immunosuppression in different infections.