DC expressing transgene Foxp3 are regulatory APC.

DC expressing transgene Foxp3 are regulatory APC.
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DOI:
10.1002/eji.200939667
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发表时间:
2010-02
影响因子:
5.4
通讯作者:
Storkus, Walter J.
Storkus, Walter J.
中科院分区:
医学3区
文献类型:
--
作者:
Lipscomb, Michael W.;Taylor, Jennifer L.;Goldbach, Cristina J.;Watkins, Simon C.;Wesa, Amy K.;Storkus, Walter J.

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耐受性树突状细胞(DC)和抑制Foxp3+ Treg在预防自身免疫和同种异体移植排斥反应中起重要作用。我们报道了(腺病毒介导的)Foxp3在人DC(即DC。Foxp3)产生抗原呈递细胞(APC),严重限制T细胞增殖和1型免疫反应naïve,但不是记忆,反应T细胞池在体外。与此形成鲜明对比的是,DC刺激naïve T细胞后,2型和调节性T细胞反应的频率显著增加。Foxp3与对照DC。直流。foxp3诱导的CD4+CD25+ Treg (XiTreg)细胞能有效抑制CD4+和CD8+应答T细胞的增殖和IFN-γ的产生。值得注意的是,DC的免疫抑制生物学。在T细胞启动期间,通过添加1-MT或中和抗tgf -β1 Ab, Foxp3有效归一化。这些数据表明了监管DC的潜在效用。Foxp3和/或DC。foxp3诱导的XiTreg作为翻译剂改善或预防同种异体移植和/或自身免疫的病理。
Tolerogenic dendritic cells (DC) and suppressive Foxp3+ Treg play important roles in preventing autoimmunity and allograft rejection. We report that (adenovirus-mediated) ectopic expression of Foxp3 in human DC (i.e. DC.Foxp3) yields an antigen presenting cell (APC) that severe limits T cell proliferation and Type 1 immune responses from the naïve, but not memory, pool of responder T cells in vitro. In marked contrast, the frequencies of Type-2 and regulatory T cell responses were dramatically increased after stimulation of naïve T cells with DC.Foxp3 vs. control DC. DC.Foxp3-induced CD4+CD25+ Treg (XiTreg) cells potently suppressed the proliferation of, and IFN-γ production from, CD4+ and CD8+ responder T cells. Notably, the immunosuppressive biology of DC.Foxp3 was effectively normalized by addition of 1-MT or neutralizing anti-TGF-β1 Ab during the period of T cell priming. These data suggest the potential utility of regulatory DC.Foxp3 and/or DC.Foxp3-induced XiTreg as translational agents for the amelioration or prevention of pathology in the setting of allograft transplantation and/or autoimmunity.
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发表时间: 1999-12-01
影响因子: 5.4
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