TGF-β regulates in vivo expansion of Foxp3-expressing CD4+CD25+ regulatory T cells responsible for protection against diabetes
TGF-β regulates in vivo expansion of Foxp3-expressing CD4+CD25+ regulatory T cells responsible for protection against diabetes
复制标题
DOI：
10.1073/pnas.0400810101
复制
发表时间：
2004-03-30
影响因子：
11.1
通讯作者：
Flavell, RA
中科院分区：
文献类型：
--
作者：
Peng, YF;Laouar, Y;Flavell, RA
CD4(+)CD25（+）调节性T细胞在器官特异性自身免疫性疾病的保护中至关重要。在胰腺中，它们抑制自身反应性T细胞的活动，从而防止糖尿病的进展。体内控制调节性T细胞库的产生、维持或扩张的信号仍然知之甚少。本研究表明，在糖尿病的启动阶段，胰岛中转化生长因子β (tgf - β)的短暂脉冲足以通过促进胰岛内CD4(+)CD25(+) T细胞池的扩张来抑制疾病的发生。大约40-50%的胰岛内CD4(+) T细胞表达CD25标记物，并表现出调节性T细胞的特征，包括小体积、高水平的细胞内CTLA-4、Foxp3的表达和对糖尿病的保护转移。BrdUrd体内掺入的结果显示，胰岛中调节性T细胞的高频产生是由于tgf - β表达的原位扩增。因此，这些发现证明了tgf - β通过调节体内CD4(+)CD25（+）调节性T细胞池的大小来抑制自身免疫性疾病的一种以前未被表征的机制。
CD4(+)CD25(+) regulatory T cells are essential in the protection from organ-specific autoimmune diseases. In the pancreas, they inhibit actions of autoreactive T cells and thereby prevent diabetes progression. The signals that control the generation, the maintenance, or the expansion of regulatory T cell pool in vivo remain poorly understood. Here we show that a transient pulse of transforming growth factor beta (TGF-beta) in the islets during the priming phase of diabetes is sufficient to inhibit disease onset by promoting the expansion of intraislet CD4(+)CD25(+) T cell pool. Approximately 40-50% of intraislet CD4(+) T cells expressed the CD25 marker and exhibited characteristics of regulatory T cells including small size, high level of intracellular CTLA-4, expression of Foxp3, and transfer of protection against diabetes. Results from in vivo incorporation of BrdUrd revealed that the generation of a high frequency of regulatory T cells in the islets is due to in situ expansion upon TGF-beta expression. Thus, these findings demonstrate a previously uncharacterized mechanism by which TGF-beta inhibits autoimmune diseases via regulation of the size of the CD4(+)CD25(+) regulatory T cell pool in vivo.