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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool
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T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool

机译:T细胞受体基因缺失圈可识别周围T细胞库中的近期胸腺迁徙

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摘要

Progenitor cells undergo T cell receptor (TCR) gene rearrangements during their intrathymic differ- entiation to become T cells. Rearrangements of the variable (V), diversity (D), and joining (J) segments of the TCR genes result in deletion of the intervening chromosomal DNA and the formation of circular episomes as a byproduct. Detection of these extrachromosomal excision circles in T cells located in the peripheral lymphoid tissues has been viewed as evidence for the existence of extrathymic T cell generation. Because all of the T cells in chickens apparently are generated in the thymus, we have employed this avian model to determine the fate of the V(D)J deletion circles. In normal animals we identified TCR V#gamma#-J#gamma# and V#beta#-D#beta# deletion circles in the blood, spleen, and intestines, as well as in the thymus. Thymectomy resulted in the gradual loss of these DNA deletion circles in all of the peripheral lymphoid tissues. A quantitative PCR anal- ysis of V#gamma#1-J#gamma#1 and V#beta#-D#beta# deletion circles in splenic #gamma##delta# and V#beta#1~+ #alpha##beta#1~+ T cells indicaled that their numbers progressively decline after thymectomy with a half-life of approximately 2 weeks. Although TCR deletion circles therefore cannot be regarded as reliable indicators of in situ V(D)J rearrangement, measuring their levels in peripheral T cell samples can provide a valuable index of newly generated T cells entering the T cell pool.
机译:祖细胞在胸腺内分化过程中经历T细胞受体(TCR)基因重排,成为T细胞。 TCR基因的可变(V),多样性(D)和连接(J)片段的重排导致插入的染色体DNA缺失并形成环状附加体作为副产物。在位于外周淋巴组织中的T细胞中对这些染色体外切除环的检测已被视为存在胸腺T细胞生成的证据。因为鸡中的所有T细胞显然都是在胸腺中产生的,所以我们采用了这种禽类模型来确定V(D)J缺失圈的命运。在正常动物中,我们在血液,脾脏和肠道以及胸腺中鉴定出了TCR V#gamma#-J#gamma#和V#beta#-D#beta#缺失圈。胸腺切除术导致所有外周淋巴组织的这些DNA缺失环逐渐丢失。脾脏#gamma ## delta#和V#beta#1〜+#alpha ##中的V#gamma#1-J#gamma#1和V#beta#-D#beta#缺失圈的定量PCR分析β#1〜+ T细胞表明,胸腺切除后它们的数量逐渐减少,半衰期约为2周。因此,尽管不能将TCR缺失圈视为原位V(D)J重排的可靠指标,但测量其在外周T细胞样品中的水平可以为进入T细胞池的新生成T细胞提供有价值的指标。

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