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Cytotoxic T‐lymphocytes recognizing P‐glycoprotein in murine multidrug‐resistant leukemias
Author(s) -
Azuma Eiichi,
Masuda Shinichi,
Qi Jiang,
Kumamoto Tadashi,
Hirayama Masahiro,
Nagai Masataka,
Hiratake Shinya,
Umemoto Masakazu,
Komada Yoshihiro,
Sakurai Minoru
Publication year - 1997
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1997.tb00954.x
Subject(s) - cytotoxic t cell , ctl* , p glycoprotein , cytotoxicity , monoclonal antibody , cd8 , multiple drug resistance , biology , leukemia , immunology , interleukin 2 , pharmacology , antibody , cytokine , immune system , drug resistance , in vitro , biochemistry , microbiology and biotechnology
A multidrug‐resistant murine lymphoid leukemia P388/ADR overexpresses P‐glycoprotein (P‐gp), an active transporter that pumps cytotoxic drugs out of cells and a product of mdr1 gene. Cytotoxic T lymphocytes (CTL) that showed cytotoxicity against P388/ADR were generated from mixed lymphocyte tumor cell culture. CTL do not kill drug‐sensitive parental P388 (P388/parent) that does not express P‐gp. Monoclonal antibody against P‐gp inhibited cytotoxic activity. Similar results were obtained in another multidrug‐resistant cell line P388/VP‐16. Cytotoxic activity was mediated by Thyl+ CD4 CD8+ T‐cells. When P388/ADR was treated with murine IL‐4, expression of P‐gp was downregulated. Monoclonal antibody against interleukin‐4 (IL‐4) abrogated the IL‐4‐induced suppression of P‐gp. Cytolytic activity of CTL against IL‐4‐treated P388/ADR was dose dependently inhibited. These results suggest that P‐gp is immunogenic and can be a target of CTL in this murine leukemia model.