Regulatory T cell lineage specification by the forkhead transcription factor FoxP3
Regulatory T cell lineage specification by the forkhead transcription factor FoxP3
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DOI：
10.1016/j.immuni.2005.01.016
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发表时间：
2005-03-01
期刊：
影响因子：
32.4
通讯作者：
Rudensky, AY
中科院分区：
文献类型：
--
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
调节性T细胞介导的显性耐受已被证明在预防自身免疫中发挥重要作用。在这里，我们提出的数据认为，叉头转录因子Foxp 3作为调节T细胞谱系规范因子和介导的遗传机制的显性耐受。我们发现Foxp 3的表达高度局限于T细胞亚群，并且与CD 25表达无关，与抑制活性相关。在病原体驱动的免疫反应期间，不会诱导非调节性T细胞中Foxp 3的表达，并且Foxp 3缺陷不会影响非调节性T细胞的功能反应。此外，Foxp 3的T细胞特异性消融足以诱导在Foxp 3缺陷小鼠中观察到的相同的早发性淋巴组织增生综合征。胸腺发育过程中Foxp 3表达的分析表明，这种机制不是硬连线，而是依赖于TCR/MHC配体相互作用。
Regulatory T cell-mediated dominant tolerance has been demonstrated to play an important role in the prevention of autoimmunity. Here, we present data arguing that the forkhead transcription factor Foxp3 acts as the regulatory T cell lineage specification factor and mediator of the genetic mechanism of dominant tolerance. We show that expression of Foxp3 is highly restricted to the subset up of T cells and, irrespective of CD25 expression, correlates with suppressor activity. Induction of Foxp3 expression in nonregulatory T cells does not occur during pathogen-driven immune responses, and Foxp3 deficiency does not impact the functional responses of nonregulatory T cells. Furthermore, T cell-specific ablation of Foxp3 is sufficient to induce the identical early onset lymphoproliferative syndrome observed in Foxp3-deficient mice. Analysis of Foxp3 expression during thymic development suggests that this mechanism is not hard-wired but is dependent on TCR/MHC ligand interactions.