Induction of antigen-specific parasiticidal cytotoxic T cell splenocytes by a major membrane protein (P30) of Toxoplasma gondii.
Infection with Toxoplasma gondii has become a major cause of morbidity in patients with AIDS. To investigate the mechanisms responsible for immune responses to toxoplasma Ag we used a highly purified membrane protein (P30) of T. gondii to stimulate an in vitro Ag-specific cytotoxic T cell response. P30 immune mouse splenocytes reduced extracellular T. gondii plaque-forming units by more than 50% when incubated at an E/T ratio of 10:1 or greater. By using a [3H]uracil radioisotope release assay, the effect of the immune splenocytes was determined to be a direct parasite lytic mechanism. The immune splenocytes were P30 Ag specific and of the Thy 1.2, Lyt2,3+ (CD4-, CD8+) phenotype, specific for mouse cytotoxic T cells. Opsonization of the parasites with monoclonal P30-reactive mAb did not enhance parasiticidal activity. Culture supernatants obtained during the 2-h cytotoxic assay were not parasiticidal, and anti-asialo-GM1 antibody plus C did not destroy the parasiticidal activity of the P30 responder cells. Accordingly, we have identified an Ag-specific subset of CD4-, CD8+, P30 responder T cells that are directly parasiticidal to extracellular T. gondii, and that exhibit cytotoxicity independent of antibody opsonization, lymphokine secretion, NK cell activity, and, apparently, MHC involvement as well.
Khan
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Department of Medicine, Dartmouth Medical School, Hanover, NH 03756.
Smith
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Kasper
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D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D015800:Protozoan Proteins; D013154:Spleen / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology*; D014122:Toxoplasma / Q000254:growth & development / Q000276:immunology*
D000953:Antigens, Protozoan; D000939:Epitopes; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; C047168:SAG1 antigen, Toxoplasma