Decrease of the Regulatory T-Cell Population by Adoptive T-Cell Transfer in a Mouse Colorectal Cancer Transplant Model

Decrease of the Regulatory T-Cell Population by Adoptive T-Cell Transfer in a Mouse Colorectal Cancer Transplant Model
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DOI:
10.3727/096504012x13340632812596
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发表时间:
2011-01-01
期刊:
影响因子:
3.1
通讯作者:
Yosikawa, Toshikazu
Yosikawa, Toshikazu
中科院分区:
医学2区
文献类型:
--
作者:
Matsumoto, Tsuguhiro;Kokura, Satoshi;Yosikawa, Toshikazu

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我们研究了过继性T细胞转移(ACT)对小鼠结直肠癌移植模型中调节性T细胞(Tcells)群体的影响。在体内研究中,在外周血、局部淋巴结和肿瘤中分析ACT后Balb/c小鼠colon 26移植模型中的Treg群体。在一项体外研究中,将CD 4(+)细胞培养在含有TGF-β的培养基中以诱导TGF-β。在此Treg诱导系统中加入或不加入LAK细胞。研究了与LAK共培养后Treg的诱导。我们还研究了IFN-γ在Treg诱导机制中的作用。ACT可显著抑制引流淋巴结和肿瘤中的T细胞增殖。与LAK细胞共培养可抑制体外T淋巴细胞的诱导。此外,通过添加外源性IFN-γ,培养的细胞中的TcR被显著抑制。此外,通过添加IFN-γ mAb增加TcR。ACT可降低肿瘤宿主的TcR。其机制之一被认为是IFN-γ抑制TcB的诱导。
We examined the effects of adoptive T-cell transfer (ACT) on the population of regulatory T cells (Tregs) in a mouse colorectal cancer transplant model. In an in vivo study, Treg populations in Balb/c mice colon26 transplant model after ACT were analyzed in peripheral blood, local lymph node, and tumor. In an in vitro study CD4(+) cells were cultured in medium containing TGF-beta to induce Tregs. LAK cells were added or not in this Treg induction system. Treg induction after coculture with LAK was investigated. We also studied the role of IFN-gamma in the mechanism of Treg induction. Tregs in the draining lymph nodes and tumor were significantly suppressed by ACT. The induction of Tregs in vitro was inhibited by coculture with LAK cells. Furthermore, Tregs in the cultured cells were significantly inhibited by addition of exogenous IFN-gamma. Moreover, Tregs were increased by addition of IFN-gamma mAb. ACT may decrease Tregs in tumor-bearing hosts. One of the mechanisms is considered to be IFN-gamma inhibiting the induction of Tregs.