Unexpectedly late expression of intracellular CD3ε and TCR γδ proteins during adult thymus development

Unexpectedly late expression of intracellular CD3ε and TCR γδ proteins during adult thymus development
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DOI:
10.1093/intimm/11.10.1641
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发表时间:
1999-10-01
影响因子:
4.4
通讯作者:
MacDonald, HR
MacDonald, HR
中科院分区:
医学3区
文献类型:
--
作者:
Wilson, A;Capone, M;MacDonald, HR

文献摘要

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在成年胸腺发育过程中,未成熟的CD 4(-)CD 8(-)[双阴性(DN)]前体细胞通过表达CD 44和CD 25定义的四个表型不同的阶段:CD 44(hi)CD 25(-)(DN 1)、CD 44(hi)CD 25(+)(DN 2)、CD 44(lo)CD 25(+)(DN 3)和CD 44(lo)CD 25(-)(DN 4)。尽管已经确定TCR β、γ和δ基因重排并与DN胸腺细胞中的CD 3组分相关地表达,但TCR和CD 3蛋白表达的精确时间尚未确定。在这份报告中,我们已经利用了一个敏感的细胞内(ic)染色技术来分析表达的ic CD 3 β,TCR β和TCR γ δ蛋白在未成熟的DN的子集。正如先前TCR β重排和mRNA表达研究所预期的,icTCR β(+)细胞首先在DN 3亚群中检测到,此后其比例增加。然而,令人惊讶的是,icCD 3 γ(+)和icTCR γ δ(+)细胞在发育后期检测到,而不是通过分子研究预测。特别是icCD 3 γ蛋白表达与从DN 2到DN 3发育阶段的过渡相一致,而icTCR γ δ蛋白表达仅在DN 4细胞的一小部分中检测到。这些发现的影响,α-β谱系分歧将进行讨论。
During adult thymus development immature CD4(-)CD8(-) [double-negative (DN)] precursor cells pass through four phenotypically distinct stages defined by expression of CD44 and CD25: CD44(hi)CD25(-) (DN1), CD44(hi)CD25(+) (DN2), CD44(lo)CD25(+) (DN3) and CD44(lo)CD25(-) (DN4). Although it is well established that the TCR beta, gamma and delta genes are rearranged and expressed in association with the CD3 components in DN thymocytes, the precise timing of expression of the TCR and CD3 proteins has not been determined. In this report we have utilized a sensitive intracellular (ic) staining technique to analyze the expression of ic CD3 epsilon, TCR beta and TCR gamma delta proteins in immature DN subsets. As expected from previous studies of TCR beta rearrangement and mRNA expression, icTCR beta(+) cells were first detected in the DN3 subset and their proportion increased thereafter. Surprisingly, however, both icCD3 epsilon(+) and icTCR gamma delta(+) cells were detected at later stages of development than was predicted by molecular studies. In particular icCD3 epsilon protein expression coincided with the transition from the DN2 to DN3 stage of development, whereas icTCR gamma delta protein expression was only detected in a minor subset of DN4 cells. The implications of these findings for alpha beta lineage divergence will be discussed.