An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires
An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires
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DOI：
10.1038/ni1318
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发表时间：
2006-04-01
影响因子：
30.5
通讯作者：
Rudensky, AY
中科院分区：
文献类型：
--
作者：
Hsieh, CS;Zheng, Y;Rudensky, AY
自我反应转录因子 Foxp3 阳性（Foxp3(+)）的调节性 T 细胞（CD4(+)CD4（+）调节性T细胞（T-调节细胞）和具有自身免疫潜能的非调节性T细胞所使用的TCR谱系之间的关系尚不清楚。在这里，我们发现 TCR beta 转基因小鼠胸腺 T-reg 细胞的 TCR 重排具有多样性，而且与外周 T-reg 细胞的重排相比，与非调节性 T 细胞的重排更为相似，这表明胸腺 T-reg 细胞对外周 T-reg 细胞群做出了重大贡献。缺乏T-调节细胞的Foxp3缺陷小鼠体内的活化T细胞 "优先 "使用Foxp3足够的TCR beta转基因小鼠体内T-调节细胞的TCR库中的TCR，这表明这些自我反应的TCR导致了Foxp3缺陷小鼠的病理变化。我们的分析表明，T-reg 细胞和潜在致病性自身免疫 T 细胞使用重叠的自身反应性 TCR。
The relationship between the T cell receptor (TCR) repertoires used by self-reactive transcription factor Foxp3-positive (Foxp3(+)) CD4(+) regulatory T cells (T-reg cells) and nonregulatory T cells with autoimmune potential is unclear. Here we found that the TCR repertoire of thymic T-reg cells in TCR beta-transgenic mice was diverse and was more similar to that of peripheral T-reg cells than that of nonregulatory T cells, suggesting that thymic T-reg cells make a substantial contribution to the peripheral T-reg cell population. Activated T cells in Foxp3-deficient mice, which lack T-reg cells, 'preferentially' used TCRs found in the TCR repertoire of T-reg cells in Foxp3-sufficient TCR beta-transgenic mice, suggesting that these self-reactive TCRs contribute to the pathology of Foxp3-deficient mice. Our analyses suggest that T-reg cells and potentially pathogenic autoimmune T cells use overlapping pools of self-reactive TCRs.