THYMOCYTE EXPRESSION OF RAG-1 AND RAG-2 - TERMINATION BY T-CELL RECEPTOR CROSS-LINKING
THYMOCYTE EXPRESSION OF RAG-1 AND RAG-2 - TERMINATION BY T-CELL RECEPTOR CROSS-LINKING
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DOI：
10.1126/science.1831564
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发表时间：
1991-08-16
期刊：
影响因子：
56.9
通讯作者：
THOMPSON, CB
中科院分区：
文献类型：
--
作者：
TURKA, LA;SCHATZ, DG;THOMPSON, CB
V（D）J [可变（多样性）连接元件]重组激活基因RAG-1和RAG-2的表达在胸腺T细胞发育过程中进行了检测。原位杂交完整的胸腺和RNA印迹分析的基础上分离的T细胞受体（TCR）表达的分离胸腺亚群表明，TCR-和TCR+皮质胸腺细胞表达RAG-1和RAG-2信使RNA的。在TCR+群体中，在未成熟的CD 4 + CD 8+（双阳性）细胞中观察到RAG表达，但在更成熟的CD 4 + CD 8-或CD 4-CD 8+（单阳性）亚群中未观察到RAG表达。因此，尽管表面带有TCR的皮质胸腺细胞继续表达RAG-1和RAG-2，但似乎这两种基因的表达在随后的胸腺成熟过程中通常终止。由于体内胸腺细胞成熟被认为是通过TCR复合物与自身主要组织相容性复合物（MHC）抗原的相互作用来调节的，这些数据表明，由TCR复合物转导的信号可能导致RAG表达的终止。与这一假设相一致，胸腺细胞TCR在体外交联导致RAG-1和RAG-2表达的快速终止，而其他T细胞表面抗原如CD 4、CD 8或HLA I类的交联没有影响。
The expression of the V(D)J [variable (diversity) joining elements] recombination activating genes, RAG-1 and RAG-2, has been examined during T cell development in the thymus. In situ hybridization to intact thymus and RNA blot analysis of isolated thymic subpopulations separated on the basis of T cell receptor (TCR) expression demonstrated that both TCR- and TCR+ cortical thymocytes express RAG-1 and RAG-2 messenger RNA's. Within the TCR+ population, RAG expression was observed in immature CD4+CD8+ (double positive) cells, but not in the more mature CD4+CD8- or CD4-CD8+ (single positive) subpopulations. Thus, although cortical thymocytes that bear TCR on their surface continue to express RAG-1 and RAG-2, it appears that the expression of both genes is normally terminated during subsequent thymic maturation. Since thymocyte maturation in vivo is thought to be regulated through the interaction of the TCR complex with self major histocompatibility complex (MHC) antigens, these data suggest that signals transduced by the TCR complex might result in the termination of RAG expression. Consistent with this hypothesis, thymocyte TCR cross-linking in vitro led to rapid termination of RAG-1 and RAG-2 expression, whereas cross-linking of other T cell surface antigens such as CD4, CD8, or HLA class I had no effect.