T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool
T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool
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DOI：
10.1073/pnas.96.4.1536
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发表时间：
1999-02-16
影响因子：
11.1
通讯作者：
Cooper, MD
中科院分区：
文献类型：
--
作者：
Kong, FK;Chen, CLH;Cooper, MD
祖细胞在其胸腺内分化期间经历T细胞受体（TCR）基因重排以成为T细胞。TCR基因的可变（V）、多样性（D）和连接（J）区段的重排导致间插染色体DNA的缺失和作为副产物的环状附加体的形成。在外周淋巴组织中的T细胞中检测到这些染色体外切除环被认为是胸腺外T细胞产生存在的证据。因为鸡的所有T细胞显然都是在胸腺中产生的，所以我们采用这种禽类模型来确定V（D）J缺失环的命运。在正常动物中，我们在血液、脾脏、肠和胸腺中鉴定了TCR V γ-J γ和V β-D β缺失环。胸腺切除术导致这些DNA缺失环在所有外周淋巴组织中逐渐丢失。对脾脏γ δ和V β 1（+）α β T细胞中V γ 1-J γ 1和V β 1-D β缺失环的定量PCR分析表明，胸腺切除术后它们的数量逐渐减少，半衰期约为2周。尽管TCR缺失环因此不能被视为原位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提供新产生的T细胞进入T细胞库的有价值的指标。
Progenitor cells undergo T cell receptor (TCR) gene rearrangements during their intrathymic differentiation 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,,ve 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 analysis of V gamma 1-J gamma 1 and V beta 1-D beta deletion circles in splenic gamma delta and V beta 1(+) alpha beta T cells indicated 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 level in peripheral T cell samples can provide a valuable index of newly generated T cells entering the T cell pool.