Granule-dependent killing of Toxoplasma gondii by CD8+ T cells.
Immunization of mice with live bradyzoites of a low-virulent Beverley strain of Toxoplasma gondii has been shown to increase CD8+ T-cell mediated immunity against a highly virulent RH strain. We found that preimmunization with an RH homogenate further enhanced this immunity. Using this model, we investigated the mechanism of CD8+ T-cell mediated protection against T. gondii infection. Splenic cells from mice immunized with RH homogenate and live bradyzoites stimulated apoptosis of RH-infected J774A.1 macrophages in vitro, and at the same time, the immunization significantly suppressed the proliferation of parasites within macrophages, as assessed by measuring 3H-uracil uptake by the parasites. Splenic cells from the immunized mice produced larger amounts of interferon-gamma (IFN-gamma) than did naive splenic cells; however, the production of nitric oxide (NO) by RH-infected macrophages was not enhanced. The elimination of CD8+ T cells from splenic cells significantly reduced their inhibitory action on parasite proliferation as well as their cytotoxic activity against RH-infected macrophages, but it did not affect the production of IFN-gamma. Treatment of CD8+ T-enriched splenic cells from the immunized mice with concanamycin A, but not an anti-Fas ligand monoclonal antibody, significantly reduced their anti-proliferative and killing capabilities, suggesting that the CD8+ T cells induced by immunization with RH antigen and live bradyzoites of the Beverley strain may exert protection against T. gondii infection at least in part through granule-dependent cytotoxic activities.
Nakano
Y
Y
Department of Parasitology and Immunology, School of Medicine, University of Tokushima, Tokushima, Japan. nakanoy@ri.imcj.go.jp
Hisaeda
H
H
Sakai
T
T
Zhang
M
M
Maekawa
Y
Y
Zhang
T
T
Nishitani
M
M
Ishikawa
H
H
Himeno
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018929:Cell Culture Techniques; D003602:Cytotoxicity, Immunologic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D007114:Immunization / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis; D018942:Macrolides; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D016052:Protozoan Vaccines / Q000276:immunology; D013154:Spleen / Q000276:immunology; D015996:Survival Rate; D014122:Toxoplasma / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000517:prevention & control; D014774:Virulence
D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D018942:Macrolides; D008562:Membrane Glycoproteins; D016052:Protozoan Vaccines; D009569:Nitric Oxide; C036978:concanamycin A; D007371:Interferon-gamma; D006180:Proton-Translocating ATPases