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.
Doolan
D L
DL
Malaria Program, Naval Medical Research Center, Bethesda, MD 20889, USA.
Hoffman
S L
SL
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