TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets.
TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets.
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基于TCR的谱系追踪：没有证据表明胰岛中天然自我抗原的常规T细胞转化为调节性T细胞。
DOI：
10.1084/jem.20070822
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发表时间：
2007-09-03
影响因子：
15.3
通讯作者：
Benoist, Christophe
中科院分区：
文献类型：
--
作者：
Wong, Jamie;Mathis, Diane;Benoist, Christophe
表达 Foxp3 的调节性 T (T reg) 细胞主要来自胸腺中的选择。然而，成熟的常规 CD4+ T (T conv) 淋巴细胞的转化可以在多种条件下实现，例如转化生长因子 β 治疗、稳态扩增或长期暴露于低剂量抗原。这种转化可能提供一种通过“转化”对自身抗原起反应的潜在损伤性 T 细胞来产生外周耐受的方法。我们在 BDC2.5 T 细胞受体 (TCR) 转基因小鼠中测试了这一假设，TCR 代表了 NOD 小鼠中天然存在的糖尿病特异性，并对胰腺自身抗原有反应。在胸腺中，在接触任何抗原之前，克隆型阳性 T reg 和 T conv 细胞表达源自内源基因座的第二条 TCRα 链。 Vα2 家族次级 TCR 的高通量单细胞测序显示，它们的 CDR3α 连接区域在 T reg 和 T conv 细胞胸腺细胞中非常不同。因此，这些特定的 CDR3α 基序提供了一个“标签”，用于测试 T 转换细胞向 T reg 细胞转换对外周自身抗原的实际影响；如果自身反应性克隆型 TCR 在胰腺或引流淋巴结中遇到同源抗原时诱导 T 转换细胞向 T reg 细胞转化，人们会期望检测到 T reg 细胞群中 T 转换细胞的标签 CDR3α 基序。对大量外周 BDC+Vα2+ 细胞进行测序表明，对该胰腺自身抗原的反应几乎没有发生转化。
Foxp3-expressing regulatory T (T reg) cells derive primarily from selection in the thymus. Yet conversion of mature conventional CD4+ T (T conv) cell lymphocytes can be achieved in several conditions, such as transforming growth factor β treatment, homeostatic expansion, or chronic exposure to low-dose antigen. Such conversion might provide a means to generate peripheral tolerance by “converting” potentially damaging T cells that react to self-antigens. We tested this hypothesis in mice transgenic for the BDC2.5 T cell receptor (TCR), which is representative of a diabetogenic specificity that is naturally present in NOD mice and reactive against a pancreatic self-antigen. In the thymus, before any exposure to antigen, clonotype-positive T reg and T conv cells express a second TCRα chain derived from endogenous loci. High-throughput single-cell sequencing of secondary TCRs of the Vα2 family showed their joining CDR3α regions to be very different in T reg and T conv cell thymocytes. These specific CDR3α motifs, thus, provided a “tag” with which to test the actual impact of T conv to T reg cell conversion in response to peripheral self-antigen; should the autoreactive clonotypic TCR induce T conv to T reg cell conversion upon encounter of cognate antigen in the pancreas or draining lymph node, one would expect to detect tag CDR3α motifs from T conv cells in the T reg cell populations. Sequencing large numbers of peripheral BDC+Vα2+ cells showed that little to no conversion occurs in response to this pancreatic autoantigen.
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影响因子：
30.5
作者：
Hsieh, CS;Zheng, Y;Rudensky, AY
通讯作者：
Rudensky, AY
通过在胰腺淋巴结中发育调节的胰岛细胞抗原的发育表现来启动自身免疫性糖尿病。
DOI：
10.1084/jem.189.2.331
发表时间：
1999-01-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Höglund P;Mintern J;Waltzinger C;Heath W;Benoist C;Mathis D
通讯作者：
Mathis D
影响因子：
15.3
作者：
Apostolou, I;von Boehmer, H
通讯作者：
von Boehmer, H
影响因子：
32.4
作者：
Correia-Neves, M;Waltzinger, C;Benoist, C
通讯作者：
Benoist, C
影响因子：
30.5
作者：
Gonzalez, A;Andre-Schmutz, I;Benoist, C
通讯作者：
Benoist, C