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Induction of Significant Cytotoxic Activity for Autologous Leukemia Cells: Inverse Correlation between Cytotoxicity and FOXP3 mRNA Expression

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Author(s): Yasuki Hijikata | Yasuhiro Maeda | Terufumi Yamaguchi | Yasuyoshi Morita | Miyako Tanaka | Chikara Hirase | Shunsuke Takai | Yoichi Tatsumi | Akihisa Kanamaru

Journal: Journal of Cancer Molecules
ISSN 1816-0735

Volume: 2;
Issue: 6;
Start page: 221;
Date: 2006;
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Keywords: acute leukemia | cytotoxicity | FOXP3 | cytotoxic T-lymphocyte | cross killing

ABSTRACT
AIM: The goal of this study is to investigate whether immunotherapy using autologous cytotoxic T-lymphocytes has become available to eradicate minimal residual disease in acute leukemia. METHODS: In this study, to generate cytotoxic T-lymphocytes (CTL), a mixed culture was carried out. Two stimulator cells, the original leukemia cells (LCs) and the new lymphoblastoid B-cell line (LCLs) established by transformation with Epstein-Barr virus, were prepared. Cytotoxic activity was examined using (1) peripheral blood mononuclear cells (PBMCs) only, (2) PBMCs plus interleukin-2, or (3) PBMCs plus LCs or LCLs plus interleukin-2. After mixed culture for 5 days, cytotoxic activity was examined by flow cytometry with PKH-26 staining. RESULTS: Interestingly, cytotoxicity to not only autologous LCs but also own LCLs was observed in most cases. There is a close relationship between the cytotoxicity to LCs and that to LCLs. This cross-killing phenomenon supports that cell therapy as an immunotherapy should be useful for improving the prognosis, and if stocked LCs is not available, effective CTL activity can be induced by a mixed culture with established own LCLs. An inverse correlation was also observed between cytotoxicity and FOXP3 mRNA expression. CONCLUSION: The generation of cytotoxic activity against autologous LCs can be induced by cultivating PBMCs with either LCs or LCLs.
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