Unraveling a revealing paradox: Why major histocompatibility complex I-signaled thymocytes "paradoxically" appear as CD4+8lo transitional cells during positive selection of CD8+ T cells.
Unraveling a revealing paradox: Why major histocompatibility complex I-signaled thymocytes "paradoxically" appear as CD4+8lo transitional cells during positive selection of CD8+ T cells.
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DOI：
10.1084/jem.20030170
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发表时间：
2003-06-16
期刊：
影响因子：
--
通讯作者：
Singer A
中科院分区：
文献类型：
--
作者：
Bosselut R;Guinter TI;Sharrow SO;Singer A
T细胞受体特异性决定胸腺CD4/CD8谱系决定结果的机制尚不清楚。一个重要的线索是，主要组织相容性复合体(MHC)- i信号胸腺细胞在向CD8+ T细胞分化过程中矛盾地表现为CD4+8lo过渡细胞。谱系承诺通常被认为发生在CD4+8+（双阳性）分化阶段，并导致相反的辅助受体基因沉默。从这个角度来看，mhc - i信号胸腺细胞出现CD4+8lo细胞可能是由于CD8表面蛋白表达的影响，而不是CD8基因表达的影响。但与这一观点相反，本研究表明mhc - i信号胸腺细胞出现CD4+8lo细胞是由于CD8基因表达的短暂下调，而不是由于CD8表面蛋白表达或分布的变化。该研究还表明，mhc - i信号胸腺细胞中CD8基因表达的初始停止并不一定表明CD4+ T细胞谱系的承诺，因为这样的胸腺细胞保留了分化为CD8+ T细胞的潜力。这些结果挑战了谱系承诺的经典概念，但实现了动力学信号模型的预测。
The mechanism by which T cell receptor specificity determines the outcome of the CD4/CD8 lineage decision in the thymus is not known. An important clue is the fact that major histocompatibility complex (MHC)-I–signaled thymocytes paradoxically appear as CD4+8lo transitional cells during their differentiation into CD8+ T cells. Lineage commitment is generally thought to occur at the CD4+8+ (double positive) stage of differentiation and to result in silencing of the opposite coreceptor gene. From this perspective, the appearance of MHC-I–signaled thymocytes as CD4+8lo cells would be due to effects on CD8 surface protein expression, not CD8 gene expression. But contrary to this perspective, this study demonstrates that MHC-I–signaled thymocytes appear as CD4+8lo cells because of transient down-regulation of CD8 gene expression, not because of changes in CD8 surface protein expression or distribution. This study also demonstrates that initial cessation of CD8 gene expression in MHC-I–signaled thymocytes is not necessarily indicative of commitment to the CD4+ T cell lineage, as such thymocytes retain the potential to differentiate into CD8+ T cells. These results challenge classical concepts of lineage commitment but fulfill predictions of the kinetic signaling model.
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