Where CD4+CD25+ T reg cells impinge on autoimmune diabetes.

Where CD4+CD25+ T reg cells impinge on autoimmune diabetes.
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DOI:
10.1084/jem.20051409
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发表时间:
2005-11-21
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Benoist C
Benoist C
中科院分区:
其他
文献类型:
--
作者:
Chen Z;Herman AE;Matos M;Mathis D;Benoist C

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Foxp3是CD4+CD25+调节性T(T reg)细胞的产生和活性所必需的,这些细胞是自身免疫(包括1型糖尿病)的重要控制者。为了确定T reg细胞影响糖尿病级联反应的位置,我们将消除T reg细胞的Foxp3 scurfy突变与BDC2.5 T细胞受体(TCR)转基因小鼠系杂交。在该模型中,T reg细胞的缺乏没有增加引流淋巴结中效应T细胞的初始活化或表型特征,也没有加速胰岛的T细胞浸润的发生。然而,这种胰岛炎立即具有破坏性,导致明显的糖尿病进展。微阵列分析显示,在胰岛病变的T reg细胞采用的基因表达程序不同的淋巴结,而T reg细胞引流或不相关的淋巴结出现非常相似。因此,T reg细胞主要通过控制胰岛内的破坏性T细胞来影响自身免疫性糖尿病,而不是在引流淋巴结中的初始激活期间。
Foxp3 is required for the generation and activity of CD4+CD25+ regulatory T (T reg) cells, which are important controllers of autoimmunity, including type-1 diabetes. To determine where T reg cells affect the diabetogenic cascade, we crossed the Foxp3 scurfy mutation, which eliminates T reg cells, with the BDC2.5 T cell receptor (TCR) transgenic mouse line. In this model, the absence of T reg cells did not augment the initial activation or phenotypic characteristics of effector T cells in the draining lymph nodes, nor accelerate the onset of T cell infiltration of the pancreatic islets. However, this insulitis was immediately destructive, causing a dramatic progression to overt diabetes. Microarray analysis revealed that T reg cells in the insulitic lesion adopted a gene expression program different from that in lymph nodes, whereas T reg cells in draining or irrelevant lymph nodes appeared very similar. Thus, T reg cells primarily impinge on autoimmune diabetes by reining in destructive T cells inside the islets, more than during the initial activation in the draining lymph nodes.
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