Distinct phases in the positive selection of CD8+ T cells distinguished by intrathymic migration and T-cell receptor signaling patterns
Distinct phases in the positive selection of CD8+ T cells distinguished by intrathymic migration and T-cell receptor signaling patterns
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DOI：
10.1073/pnas.1408482111
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发表时间：
2014-06-24
影响因子：
11.1
通讯作者：
Robey, Ellen A.
中科院分区：
文献类型：
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作者：
Ross, Jenny O.;Melichar, Heather J.;Robey, Ellen A.
胸腺中CD 8 T细胞的阳性选择被认为是一个持续3-4天的多步骤过程;然而，所涉及的离散步骤知之甚少。在这里，我们研究表型的变化，钙信号，和胸腺内迁移在一个同步队列的MHC I类特异性胸腺细胞进行积极的选择原位。细胞内钙浓度（[Ca 2 +]（i））的短暂升高和迁移暂停发生在阳性选择的前24小时，随着时间的推移，逐渐变得短暂，并伴随着基础[Ca 2 +]（i）的逐渐变化。趋化因子受体表达的变化和从皮质到髓质的重新定位发生在与阳性选择配体初次相遇后12至24小时之间，在这个时间范围内，大多数胸腺细胞保留CD 4和CD 8表达，并且仍然需要T细胞受体（TCR）信号传导来有效地完成阳性选择。我们的研究结果确定了不同的阶段，在积极选择的MHC I类特异性胸腺细胞，区分其TCR信号模式和胸腺内的位置，并提供了一个框架，了解积极选择在胸腺的多步骤过程。
Positive selection of CD8 T cells in the thymus is thought to be a multistep process lasting 3-4 d; however, the discrete steps involved are poorly understood. Here, we examine phenotypic changes, calcium signaling, and intrathymic migration in a synchronized cohort of MHC class i-specific thymocytes undergoing positive selection in situ. Transient elevations in intracellular calcium concentration ([Ca2+](i)) and migratory pauses occurred throughout the first 24 h of positive selection, becoming progressively briefer and accompanied by a gradual shift in basal [Ca2+](i) over time. Changes in chemokine-receptor expression and relocalization from the cortex to medulla occurred between 12 and 24 h after the initial encounter with positive-selecting ligands, a time frame at which the majority of thymocytes retain CD4 and CD8 expression and still require T-cell receptor (TCR) signaling to efficiently complete positive selection. Our results identify distinct phases in the positive selection of MHC class I-specific thymocytes that are distinguished by their TCR-signaling pattern and intrathymic location and provide a framework for understanding the multistep process of positive selection in the thymus.