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We previously generated transgenic mice that express the complementary DNA of a chimeric receptor composed of the extracellular binding domain of CD4 and the transmembrane and cytoplasmic domains of CD8. The chimeric receptor was specifically expressed on CD4+ T cells, and the CD4+ T cells in these mice were resistant to Fas-mediated apoptosis. Here, we directly injected chimeric receptor-expressing T cells transfected with either a constitutive retroviral vector expressing the human Fas ligand, or a retroviral vector expressing the human Fas ligand, into hosts expressing the Fas receptor or Fas-ligand, and we examined apoptosis in these chimeric T cell populations. Apoptosis in the transfectants occurred in a Fas- and dose-dependent manner. Fas ligand-transfected cells were specifically killed in a CD95-dependent manner, and this cytotoxic activity was mediated by Fas ligand binding to Fas. Fas ligand-transfected T cells and wild-type T cells of CD4+/CD8+ phenotype were resistant to Fas-mediated apoptosis, while Fas ligand-expressing cells were killed by Fas-expressing cells. From these results, we conclude that the T cells that express chimeric receptors are resistant to Fas-mediated apoptosis.Kallemic Acid, an Epipodophyllotoxin Derivative, Shows Antileukemic Potential and Sensitivity to B-Raf Kinase Inhibitors.
Natural epipodophyllotoxins are cytotoxic macrolides that are produced by the South American Hypogymniaceae Epiphyllum family. In recent years, studies have focused on the isolation and identification of new natural epipodophyllotoxins, and
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