Azuma E, Masuda S, Qi J, Kumamoto T, Hirayama M, Nagai M, Hiratake S, Umemoto M, Komada Y, Sakurai M
Department of Pediatrics and Clinical Immunology, Mie University School of Medicine, Japan.
Eur J Haematol. 1997 Jul;59(1):14-9. doi: 10.1111/j.1600-0609.1997.tb00954.x.
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 drugsensitive 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 Thy1+ 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.
一种多药耐药的小鼠淋巴细胞白血病P388/ADR过度表达P-糖蛋白（P-gp），P-糖蛋白是一种主动转运蛋白，可将细胞毒性药物泵出细胞，是mdr1基因的产物。通过混合淋巴细胞肿瘤细胞培养产生了对P388/ADR具有细胞毒性的细胞毒性T淋巴细胞（CTL）。CTL不会杀死不表达P-gp的药物敏感亲本P388（P388/亲本）。抗P-gp单克隆抗体抑制细胞毒性活性。在另一种多药耐药细胞系P388/VP-16中也获得了类似结果。细胞毒性活性由Thy1+ CD4- CD8+ T细胞介导。用小鼠IL-4处理P388/ADR后，P-gp的表达下调。抗白细胞介素-4（IL-4）单克隆抗体消除了IL-4诱导的P-gp抑制作用。CTL对IL-4处理的P388/ADR的细胞溶解活性受到剂量依赖性抑制。这些结果表明，在这种小鼠白血病模型中，P-gp具有免疫原性，可成为CTL的靶标。
