CD4+ and CD8+ T lymphocytes both contribute to acquired immunity to blood-stage Plasmodium chabaudi AS

Abstract

In the present study, the contribution of CD4+ and CD8+ T lymphocytes to acquired immunity to blood-stage infection with the murine malaria species Plasmodium chabaudi AS was investigated. C57BL/6 mice, which are genetically resistant to infection with this hemoprotozoan parasite and exhibit a transient course of infection, were treated intraperitoneally with monoclonal antibodies to T-cell epitopes, either anti-Thy-1, anti-CD4, or anti-CD8. After intraperitoneal infection with 10(6) parasitized erythrocytes, control C57BL/6 mice exhibited a peak parasitemia on day 9 of approximately 35% parasitized erythrocytes and eliminated the infection within 4 weeks. Mice depleted of Thy-1+ or CD4+ T cells had significantly higher parasitemias on day 7 as well as significantly higher peak parasitemias. These mice were unable to control the infection and developed a persistent, high parasitemia that fluctuated between 40 and 60% until the experiment was terminated on day 56 postinfection. Depletion of CD8+ T lymphocytes was found to have no effect on the early course of parasitemia or on the level of peak parasitemia. However, mice depleted of CD8+ T cells experienced two recurrent bouts of parasitemia during the later stage of the infection and required more than 5 weeks to eliminate the parasites. After the peak parasitemia, which occurred in control and experimental animals on day 9, there was a sharp drop in parasitemia coinciding with a wave of reticulocytosis. Therefore, the contribution of the influx of reticulocytes, which are not the preferred host cell of this hemoprotozoan parasite, to limiting the parasitemia was also examined by determining the course of reticulocytosis during infection in control and T cell-depleted animals. Early in infection, there was a marked and comparable reticulocytosis in the peripheral blood of control and T cell-depleted mice; the reticulocytosis peaked on day 12 and coincided with the dramatic and sudden reduction in parasitemia occurring in all groups. In both control and CD8-depleted mice the percentage of reticulocytes decreased as the infection was resolved, whereas in CD4-depleted mice marked reticulocytosis correlated with high, persistent parasitemia. These results thus demonstrate that both CD4+ and CD8+ T cells are involved in acquired immunity to blood-stage P. chabaudi AS and that the influx of reticulocytes into the blood that occurs just after the peak parasitemia may contribute temporarily to limiting the parasitemia.