Perforin-dependent cytolytic responses in beta2-microglobulin-deficient mice.
The ability of beta2-microglobulin-deficient mice (B6.beta2micro(o)) mice to reject syngeneic and major histocompatability (MHC) class I-deficient tumor grafts was examined with a view to determining residual cytotoxic activities that exist in these mice. In particular, the cytotoxic activities of NK cells and CD8(+) cytotoxic T lymphocytes (CTL) reactive against self-MHC class I were assessed using a variety of gene-targeted mice. The creation of mice doubly deficient for perforin and beta2micro (B6.P(o).beta2micro(o)) enabled the determination that perforin was responsible for the cytotoxic activity of NK cells and CD8(+) CTL reactive against self-MHC class I. Dependence on perforin function was demonstrated for the cytotoxicity of these effectors in vitro and for the ability of these effectors to reject a variety of tumors in vivo.
Smyth
M J
MJ
Cellular Cytotoxicity Laboratory, The Austin Research Institute, Studley Road, Heidelberg, Victoria, 3084, Australia. m.smyth@ari.unimelb.edu.au
Snook
M B
MB
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology; D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology; D000954:Antigens, Surface; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type; D008285:Major Histocompatibility Complex; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009368:Neoplasm Transplantation / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology*
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000941:Antigens; D000954:Antigens, Surface; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; C489516:Tap2 protein, mouse; D001613:beta 2-Microglobulin; D054353:Perforin