AFRICAN TRYPANOSOME INFECTIONS IN MICE THAT LACK THE INTERFERON-GAMMARECEPTOR GENE - NITRIC OXIDE-DEPENDENT AND OXIDE-INDEPENDENT SUPPRESSION OF T-CELL PROLIFERATIVE RESPONSES AND THE DEVELOPMENT OF ANEMIA

Infection of mice with African trypanosomes leads to a severe immunosu ppression, mediated by suppressor macrophages. Using ex vivo macrophag e culture and in vivo cell transfer, it has been shown that nitric oxi de (NO) is a potent effector product of these cells and causes both ly mphocyte unresponsiveness and dyserythropoiesis. We explored the role of NO in vivo during trypanosome infection using mice with a disrupted interferon-gamma-receptor gene, which were unable to respond with mac rophage activation and NO synthesis. These mice were less effective at controlling parasitaemia than the wild types, but showed an improved splenic T-cell responsiveness and reduced anaemia during the early sta ges of infection. The data indicate that, in the mouse, NO is a signif icant mediator of immunosuppression only in early infection. Beyond da y 10 of infection, NO-independent mechanisms are of primary significan ce and the control of parasitaemia and T-cell responsiveness are not d irectly related.