The role of gamma interferon (IFN-y), a pluripotent lymphokine capable of activating macrophages, in acquired immunity to blood-stage malaria was investigated. C57BL-derived, lipopolysaccharride-resistant C57BL/lOScN mice, which were found to be resistant to intraperitoneal (i.p.) infection with 106 Plasmodium chabaudi AS parasitized erythrocytes, were treated with monoclonal anti-IFN-7y antibody (MAb). Two MAbs were used: R4-6A2, a rat anti-mouse, neutralizing immunoglobulin Gl, which was

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... red against natural murine IFN--y, and DB-1, a murine anti-rat immunoglobulin Gl prepared against recombinant rat IFN--y, which can neutralize the murine molecule as well as the rat molecule. C57BL/10ScNH mice were injected i.p. with 200 ,ug of R4-6A2 1 day before infection and every 3 days through day 21. Control mice were treated with normal rat serum. In separate experiments, DB-1 (1.0 mg per week for 4 weeks) was administered i.p. to C57BL/lOScNH mice beginning on the day of infection; control mice were untreated. Control and MAb-treated mice were infected i.p. with 106 P. chabaudi AS parasitized erythrocytes, and the course and outcome of infection were determined. Control mice exhibited a course of infection that was characterized by a peak parasitemia between 30 and 40% parasitized erythrocytes and elimination of the parasite by 4 weeks. MAb-treated mice exhibited a significantly greater parasitemia 1 to 2 days before the peak parasitemia as well as a significantly greater peak parasitemia but also completely cleared the infection by 4 weeks. Thus, these results suggest that treatment with anti-IFN-y MAb impairs but does not completely abrogate host resistance to P. chabaudi AS. We also examined the kinetics of IFN-y production by spleen cells cultured in vitro with malaria antigen or concanavalin A. Spleen cells were recovered from individual C57BL/6 mice at various times on May 8, 2020 by guest http://iai.asm.org/ Downloaded from