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人外周血T细胞中重组激活基因的持续表达及TCR基因重组

Continued expression of recombination-activating genes and TCR gene recombination in human peripheral T cells.

作者信息

Li Tong-Tong, Han Shuhua, Cubbage Mike, Zheng Biao

机构信息

Department of Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

出版信息

Eur J Immunol. 2002 Oct;32(10):2792-9. doi: 10.1002/1521-4141(2002010)32:10<2792::AID-IMMU2792>3.0.CO;2-I.

Abstract

It has been reported that a small population of peripheral T lymphocytes are capable of expressing V(D)J recombinase and initiating secondary V(D)J rearrangements. To determine whether RAG-expression and secondary TCR gene recombination in peripheral T cells are an antigen-driven process in secondary lymphoid tissues, we examined naive CD4(+) T cells, activated/memory CD4(+) T cells, and germinal center T cells from human tonsils. Our results showed that low levels of RAG-1 and RAG-2 mRNA were present in all T cell subpopulations except CD3(+)/CD4(-) T cells. LM-PCR analyses for double-strand DNA breaks showed that all the T cell subsets expressing RAG genes contain double-strand signal break ends, indicating ongoing TCR gene recombination. Continued RAG gene expression, introducing and repairing of double-strand DNA breaks at the TCR loci in the periphery may have significant implications in the development of some T cell neoplasms.

摘要

据报道,一小部分外周血T淋巴细胞能够表达V(D)J重组酶并启动继发性V(D)J重排。为了确定外周血T细胞中RAG表达和继发性TCR基因重组是否是次级淋巴组织中的抗原驱动过程,我们检测了人扁桃体中的初始CD4(+) T细胞、活化/记忆CD4(+) T细胞和生发中心T细胞。我们的结果显示,除了CD3(+)/CD4(-) T细胞外,所有T细胞亚群中均存在低水平的RAG-1和RAG-2 mRNA。对双链DNA断裂的连接介导PCR(LM-PCR)分析表明,所有表达RAG基因的T细胞亚群均含有双链信号断裂末端,表明正在进行TCR基因重组。外周血中RAG基因的持续表达、TCR基因座处双链DNA断裂的引入和修复可能对某些T细胞肿瘤的发生具有重要意义。

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