Exogenous IFN-gamma ex vivo shapes the alloreactive T-cell repertoire by inhibition of Th17 responses and generation of functional Foxp3+ regulatory T cells.
Exogenous IFN-gamma ex vivo shapes the alloreactive T-cell repertoire by inhibition of Th17 responses and generation of functional Foxp3+ regulatory T cells.
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DOI：
10.1002/eji.200838411
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发表时间：
2008-09
影响因子：
5.4
通讯作者：
Bushell, Andrew
中科院分区：
文献类型：
--
作者：
Feng, Gang;Gao, Wenda;Strom, Terry B.;Oukka, Mohamed;Francis, Ross S.;Wood, Kathryn J.;Bushell, Andrew
干扰素-γ最初被认为是一种具有T辅助细胞1型诱导活性的促炎细胞因子，但后来的研究表明，干扰素-γ或干扰素-γ受体缺陷的小鼠表现出炎症反应加剧和同种异体排斥反应加速，提示干扰素-γ也具有重要的免疫调节功能。在这里，我们证明了体外干扰素-γ对同种异体未成熟树突状细胞(DC)驱动的CD4T细胞的调节，导致了以Foxp3+调节性T细胞(Treg)为主的群体的出现，可以防止同种异体移植排斥反应。这一群体的发展包括非Treg前体的转换，在非Treg群体中优先诱导激活诱导的细胞死亡，以及抑制Th2和Th17反应。干扰素-γ的抑制作用依赖于转录因子信号转导和转录激活因子1，并由诱导型一氧化氮介导。这些数据表明，干扰素-γ不仅可以用于在体外形成有益的免疫反应，用于可能的细胞治疗，而且还提供了一些可能与几种自身免疫和移植模型中存在干扰素-γ缺陷的炎症反应加剧有关的机制见解。
Interferon (IFN)-γ was originally characterized as a pro-inflammatory cytokine with T helper type 1-inducing activity, but subsequent work has demonstrated that mice deficient in IFN-γ or IFN-γ receptor show exacerbated inflammatory responses and accelerated allograft rejection, suggesting that IFN-γ also has important immunoregulatory functions. Here, we demonstrate that ex vivo IFN-γ conditioning of CD4 T cells driven by allogeneic immature dendritic cells (DC) results in the emergence of a Foxp3+ regulatory T-cell (Treg)- dominant population that can prevent allograft rejection. The development of this population involves conversion of non-Treg precursors, preferential induction of activation-induced cell death within the non-Treg population and suppression of Th2 and Th17 responses. The suppressive activity of IFN-γ is dependent on the transcription factor signal transducer and activator of transcription 1 and is mediated by induced nitric oxide. These data indicate not only how IFN-γ could be used to shape beneficial immune responses ex vivo for possible cell therapy but also provide some mechanistic insights that may be relevant to exacerbated inflammatory responses noted in several autoimmune and transplant models with IFN-γ deficiency.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
T-BET的丧失，但不是STAT1阻止了实验性自身免疫性脑脊髓炎的发展。
影响因子：
15.3
作者：
Bettelli, E;Sullivan, B;Szabo, SJ;Sobel, RA;Glimcher, H;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
15.9
作者：
Guillonneau, Carole;Hill, Marcelo;Anegon, Ignacio
通讯作者：
Anegon, Ignacio
影响因子：
30.5
作者：
Grohmann, U;Orabona, C;Puccetti, P
通讯作者：
Puccetti, P
影响因子：
4.4
作者：
Bishop, DK;Wood, SC;Orosz, CG
通讯作者：
Orosz, CG