IL-12 and NK cells are required for antigen-specific adaptive immunity against malaria initiated by CD8+ T cells in the Plasmodium yoelii model.
CD8+ T cells have been implicated as critical effector cells in protection against preerythrocytic stage malaria, including the potent protective immunity of mice and humans induced by immunization with radiation-attenuated Plasmodium spp. sporozoites. This immunity is directed against the Plasmodium spp. parasite developing within the host hepatocyte and for a number of years has been presumed to be mediated directly by CD8+ CTL or indirectly by IFN-gamma released from CD8+ T cells. In this paper, in BALB/c mice, we establish that after immunization with irradiated sporozoites or DNA vaccines parasite-specific CD8+ T cells trigger a novel mechanism of adaptive immunity that is dependent on T cell- and non-T cell-derived cytokines, in particular IFN-gamma and IL-12, and requires NK cells but not CD4+ T cells. The absolute requirement for CD8+ T cells to initiate such an effector mechanism, and the requirement for IL-12 and NK cells in such vaccine-induced protective immunity, are unique and underscore the complexity of the immune responses that protect against malaria and other intracellular pathogens.
Malaria Program, Naval Medical Research Center, Bethesda, MD 20889, USA.
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Doolan
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Hoffman
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000469:parasitology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D017780:Malaria Vaccines / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology; D010967:Plasmodium yoelii / Q000254:growth & development / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000469:parasitology; D019444:Vaccines, DNA / Q000276:immunology
D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D019444:Vaccines, DNA; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma