Abstract
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.
Copyright 1999 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 3
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / immunology
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Adoptive Transfer
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Animals
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Antigens / immunology
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Antigens, Surface
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CD8-Positive T-Lymphocytes / immunology
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Cells, Cultured
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Cytotoxicity, Immunologic / immunology*
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H-2 Antigens / immunology
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Histocompatibility Antigen H-2D
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Histocompatibility Antigens Class I / immunology
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Killer Cells, Natural / immunology
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Lectins, C-Type
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Major Histocompatibility Complex
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, SCID
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NK Cell Lectin-Like Receptor Subfamily B
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Neoplasm Transplantation / immunology
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Perforin
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Pore Forming Cytotoxic Proteins
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Proteins / immunology
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T-Lymphocytes, Cytotoxic / immunology
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Tumor Cells, Cultured
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beta 2-Microglobulin / genetics
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beta 2-Microglobulin / immunology*
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 3
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ATP-Binding Cassette Transporters
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Antigens
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Antigens, Surface
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H-2 Antigens
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H-2Kb protein, mouse
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Histocompatibility Antigen H-2D
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Histocompatibility Antigens Class I
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Lectins, C-Type
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Membrane Glycoproteins
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NK Cell Lectin-Like Receptor Subfamily B
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Pore Forming Cytotoxic Proteins
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Proteins
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Tap2 protein, mouse
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beta 2-Microglobulin
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Perforin