Cutting edge: Regulatory T cells selectively attenuate, not terminate, T cell signaling by disrupting NF-κB nuclear accumulation in CD4 T cells.
Cutting edge: Regulatory T cells selectively attenuate, not terminate, T cell signaling by disrupting NF-κB nuclear accumulation in CD4 T cells.
复制标题
DOI：
10.4049/jimmunol.1101027
复制
发表时间：
2012-02-01
期刊：
影响因子：
--
通讯作者：
Fowell DJ
中科院分区：
文献类型：
--
作者：
Huang YH;Sojka DK;Fowell DJ
调节性T细胞（Treg）抑制CD 4 T细胞的一个关键结果是抑制IL-2的产生，但尚未确定Treg如何减弱IL-2。目前的模型预测TCR信号传导的终止，通过破坏T-APC接触，或TCR信号修饰，通过如cAMP的机制。为了直接定义Treg对CD 4 T细胞靶点中TCR信号传导的影响，我们观察了IL-2被主动抑制时转录因子核积聚的变化。NFAT的核积累高度依赖于靶中持续的TCR信号传导。然而，在TdR的存在下，NFAT和AP-1信号在靶细胞中持续。相反，NFκB p65选择性减弱。因此，TCR通常不终止TCR信号。相反，TCR 4在与CD 4靶点接触数小时内选择性调节TCR信号，不依赖于APC，导致NFκB p65信号的特异性丧失。
A key consequence of regulatory T cell (Treg) suppression of CD4 T cells is the inhibition of IL-2 production, yet how Tregs attenuate IL-2 has not been defined. Current models predict a termination of TCR signaling, by disrupting T-APC contacts, or TCR-signal modification, through mechanisms such as cAMP. To directly define Treg effects on TCR signaling in CD4 T cell targets we visualized changes in nuclear accumulation of transcription factors at timepoints when IL-2 was actively suppressed. Nuclear accumulation of NFAT was highly dependent on sustained TCR signaling in the targets. However, in the presence of Tregs, NFAT and AP-1 signals were sustained in the target cells. In contrast, NFκB p65 was selectively attenuated. Thus Tregs do not generally terminate TCR signals. Rather, Tregs selectively modulate TCR signals within hours of contact with CD4 targets, independent of APC, resulting in the specific loss of NFκB p65 signals.
登录
查看更多内容
影响因子：
64.8
作者：
Wolfe, SA;Zhou, P;Verdine, GL
通讯作者：
Verdine, GL
影响因子：
11.4
作者：
Macián, F;García-Rodríguez, C;Rao, AJN
通讯作者：
Rao, AJN
影响因子：
4.4
作者：
Sojka, DK;Hughson, A;Fowell, DJ
通讯作者：
Fowell, DJ
影响因子：
5.4
作者：
Bodor, Josef;Fehervari, Zoltan;Sakaguchi, Shimon
通讯作者：
Sakaguchi, Shimon
影响因子：
32.4
作者：
Gri G;Piconese S;Frossi B;Manfroi V;Merluzzi S;Tripodo C;Viola A;Odom S;Rivera J;Colombo MP;Pucillo CE
通讯作者：
Pucillo CE