Resolution of acute malarial infections by T cell-dependent non-antibody-mediated mechanisms of immunity.

While it is generally accepted that acute blood stage malarial infections are resolved through the actions of protective antibodies, we observed that resistance to acute infection with Plasmodium chabaudi adami was mediated by T cell-dependent cellular immune mechanisms independent of antibody. We now report that acute blood stage infections caused by three additional murine hemoprotozoan parasites, Plasmodium vinckei petteri, Plasmodium chabaudi chabaudi, and Babesia microti, appear to be controlled by similar T cell-dependent mechanisms of immunity. Mice rendered B cell deficient by lifelong treatment with goat anti-mouse immunoglobulin M (IgM) had IgM levels in serum of less than 0.6 micrograms/ml and contained precipitating amounts of goat anti-mouse IgM. When these B cell-deficient mice were infected with blood stage P. vinckei petteri, P. chabaudi chabaudi, or B. microti, they resolved their infections with kinetics similar to those seen in immunologically intact mice. Infected B cell-deficient mice did not produce antiparasite antibodies. As assayed by immunofluorescence, significant titers of parasite-specific antibody were present only in the sera of infected immunocompetent mice. In addition, only sera from infected immunocompetent mice immunoprecipitated metabolically labeled parasite antigens. In contrast to B cell-deficient mice, athymic nude mice failed to resolve acute P. vinckei petteri or B. microti infections. These data suggest that antibody-independent, T cell-mediated immune mechanisms play a more significant role in resisting acute blood stage infections caused by hemoprotozoa than was recognized previously.