Expression of B7-1 by highly metastatic mouse T lymphomas induces optimal natural killer cell-mediated cytotoxicity.
The interaction between B7-1 and CD28 provides costimulatory signals not only for T cells but also for natural killer (NK) cells. Highly metastatic mouse T lymphoma cells (BW-Li) can escape from NK cell-mediated killing by expressing H-2Dk molecules that negatively regulate NK lytic activity. We have analyzed whether B7-1:CD28 overrules the MHC class I-mediated inactivation of NK cells by transfecting BW-Li with the gene coding for B7-1. Expression of B7-1 rendered BW-Li cells sensitive toward NK cells. The experimental metastatic capacity of the B7-1 transfectants was drastically reduced in both syngeneic AKR and SCID mice but could be restored in SCID-bg mice. These results provide direct evidence that B7-1 expression leads to NK-mediated elimination of metastasizing, NK-resistant tumor cells.
Geldhof
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AB
Laboratory of Cellular Immunology, Flemish Institute for Biotechnology, Free University of Brussels, Sint Genesius Rode.
Raes
G
G
Bakkus
M
M
Devos
S
S
Thielemans
K
K
De Baetselier
P
P
D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D007111:Immunity, Cellular; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D016399:Lymphoma, T-Cell / Q000276:immunology*; D051379:Mice; D008806:Mice, Inbred AKR; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000276:immunology
D018122:B7-1 Antigen; D006183:H-2 Antigens