Kinetics of T cell receptor β, γ, and δ rearrangements during adult thymic development:: T cell receptor rearrangements are present in CD44+CD25+ Pro-T thymocytes

Kinetics of T cell receptor β, γ, and δ rearrangements during adult thymic development:: T cell receptor rearrangements are present in CD44+CD25+ Pro-T thymocytes
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DOI:
10.1073/pnas.95.21.12522
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发表时间:
1998-10-13
影响因子:
11.1
通讯作者:
Zlotnik, A
Zlotnik, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Capone, M;Hockett, RD;Zlotnik, A

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我们对小鼠成年胸腺 T 细胞前体中的 T 细胞受体 (TCR) γ 重排进行了全面分析。使用灵敏的定量PCR方法,我们发现CD44(+)CD25(+) Pro-T胸腺细胞中出现TCR γ重排的时间比预期早得多。 TCR γ 重排从 Pro-T 到 CD44(-)CD25(+) Pre-T 细胞转变显着增加,并且根据每个 V γ 基因片段遵循不同的模式,表明成年小鼠胸腺中存在 TCR γ 重排的有序波,正如在胎儿小鼠胸腺中所描述的那样。 TCR gamma 基因的重组与 TCR delta 和 D-JP 重排同时发生,但在 VP 基因组装之前。富有成效的 TCR γ 重排在前 T 细胞阶段之前不会显着增加,并且在正常小鼠的 CD4(+)CD8(+) 双阳性细胞中被耗尽。相比之下,来自 TCR delta-/- 小鼠的双阳性胸腺细胞显示出随机比例的 TCR gamma 重排等位基因,支持功能性 TCR gamma/delta 重排在 y delta 分歧过程中的作用。
We performed a comprehensive analysis of T cell receptor (TCR) gamma rearrangements in T cell precursors of the mouse adult thymus. Using a sensitive quantitative PCR method, we show that TCR gamma rearrangements are present in CD44(+)CD25(+) Pro-T thymocytes much earlier than expected. TCR gamma rearrangements increase significantly from the Pro-T to the CD44(-)CD25(+) Pre-T cell transition, and follow different patterns depending on each V gamma gene segment, suggesting that ordered waves of TCR gamma rearrangement exist in the adult mouse thymus as has been described in the fetal mouse thymus. Recombinations of TCR gamma genes occur concurrently with TCR delta and D-JP rearrangements, but before VP gene assembly. productive TCR gamma rearrangements do not increase significantly before the Pre-T cell stage and are depleted in CD4(+)CD8(+) double-positive cells from normal mice. In contrast, double-positive thymocytes from TCR delta-/- mice display random proportions of TCR gamma rearranged alleles, supporting a role for functional TCR gamma/delta rearrangements in the y delta divergence process.