Local effects of regulatory T cells in MUC1 transgenic mice potentiate growth of MUC1 expressing tumor cells in vivo.
Local effects of regulatory T cells in MUC1 transgenic mice potentiate growth of MUC1 expressing tumor cells in vivo.
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DOI：
10.1371/journal.pone.0044770
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Irimura T
中科院分区：
文献类型：
--
作者：
Sugiura D;Denda-Nagai K;Takashima M;Murakami R;Nagai S;Takeda K;Irimura T
MUC1转基因(MUC1.Tg)小鼠已被广泛用于MUC1肿瘤免疫治疗的模型受体。尽管MUC1.Tg小鼠先前已被证明对MUC1具有免疫耐受性，但调节性T(Treg)细胞参与这一表型尚不清楚。在这里，我们发现在MUC1.Tg小鼠中表达MUC1的肿瘤中Treg细胞的数量多于对照C57BL/6(B6)小鼠，并且表达MUC1的肿瘤细胞在MUC1中的生长，但不是对照细胞的生长。Tg小鼠比B6小鼠更快。MUC1.Tg小鼠似乎形成了MUC1特异性外周免疫耐受，因为转移的MUC1特异性T细胞在MUC1.Tg小鼠中无法发挥功能，但在对照B6小鼠中具有功能。在体外比较Treg细胞对MUC1特异性T细胞的杀伤活性时，来自MUC1Tg小鼠的CD4+CD25High细胞比来自对照B6小鼠的细胞具有更强的抑制功能。因此，MUC1Tg小鼠体内表达MUC1Tg的肿瘤细胞生长增强可能是由于MUC1特异性Treg细胞的存在。
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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