Local Effects of Regulatory T Cells in MUC1 Transgenic Mice Potentiate Growth of MUC1 Expressing Tumor Cells In Vivo
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| Authors: | Daisuke Sugiura Kaori Denda-Nagai Mitsuyo Takashima Ryuichi Murakami Shigenori Nagai Kazuyoshi Takeda Tatsuro Irimura |
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| Institution: | 1. Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Tokyo, Japan.; 2. Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.; 3. Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.; University of Pittsburgh, United States of America, |
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| Abstract: | MUC1 transgenic (MUC1.Tg) mice have widely been used as model recipients of cancer immunotherapy with MUC1. Although MUC1.Tg mice have previously been shown to be immunologically tolerant to MUC1, the involvement of regulatory T (Treg) cells in this phenotype remains unclear. Here, we showed that numbers of Treg cells in MUC1-expressing tumors were greater in MUC1.Tg mice than in control C57BL/6 (B6) mice, and that the growth of tumor cells expressing MUC1, but not that of control cells, in MUC1. Tg mice was faster than in B6 mice. The MUC1.Tg mice appeared to develop MUC1-specific peripheral tolerance, as transferred MUC1-specific T cells were unable to function in MUC1.Tg mice but were functional in control B6 mice. The suppressive function of CD4+CD25high cells from MUC1.Tg mice was more potent than that of cells from control B6 mice when Treg cell activity against MUC1-specific T cells was compared in vitro. Therefore, the enhanced growth of MUC1-expressing tumor cells in MUC1.Tg mice is likely due to the presence of MUC1-specific Treg cells. |
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