A purified parasite antigen (p30) mediates CD8+ T cell immunity against fatal Toxoplasma gondii infection in mice.
Induction of protective immunity against acute and chronic toxoplasmosis can be achieved using p30, the major membrane and excreted/secreted protein of Toxoplasma gondii. This protein, when administered to outbred mice in the presence of the saponin Quil A, is able to induce almost 100% protection against acute infection without evidence of intracerebral cyst development. Adoptive transfer of immune splenocytes from immunized inbred A/J mice conferred a significant level (p less than 0.001) of protection against subsequent challenge. Phenotypic analysis in outbred as well as two different strains of inbred mice (A/J and C57BL/6) demonstrated that CD8+ T cells are selectively stimulated by this immunization protocol. T cell depletion studies using specific mAb directed at either CD3+ or CD8+ T cell phenotype, followed by adoptive transfer, failed to confer protective immunity, whereas CD4+ depletion had no effect. These cytotoxic CD8+ T cells produced high titers of both IFN-gamma and IL-2. Moreover, these CD8+ T cells were directly parasiticidal against radiolabeled extracellular T. gondii, further supporting the critical immune function of these p30 Ag-specific CD8+ T cells in host immunity against T. gondii infection.
Department of Medicine, Dartmouth Medical School, Hanover, NH 03756.
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D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology*; D062605:Quillaja Saponins; D012503:Saponins / Q000008:administration & dosage; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D016827:CD8 Antigens; D007376:Interleukin-2; D015800:Protozoan Proteins; D062605:Quillaja Saponins; C047168:SAG1 antigen, Toxoplasma; D012503:Saponins; C046386:Quil A; D007371:Interferon-gamma