The peripheral maturation of human CD1d-restricted natural killer T (NKT) cells has not been well described. In this study, we identified four major subsets of NKT cells in adults, distinguished by the expression of CD4, CD8 and CCR5. Phenotypic analysis suggested a hierarchical pattern of differentiation, whereby immature CD4+ CD8- CCR5- cells progressed to an intermediate CD4+ CD8- CCR5+ stage, which remained less differentiated than the CD4- CD8- and CD4- CD8+ subsets, both of which expressed CCR5. This interpretation was supported by functional data, including clonogenic potential and cytokine secretion profiles, as well as T-cell receptor (TCR) excision circle analysis. Moreover, conventional and high-throughput sequencing of the corresponding TCR repertoires demonstrated significant clonotypic overlap within individuals, especially between the more differentiated CD4- CD8- and CD4- CD8+ subsets. Collectively, these results mapped a linear differentiation pathway across the post-thymic landscape of human CD1d-restricted NKT cells.

中文翻译：

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人类自然杀伤T细胞的外周分化。

人类CD1d限制的自然杀伤T细胞（NKT）的外围成熟还没有很好的描述。在这项研究中，我们确定了成人NKT细胞的四个主要亚群，以CD4，CD8和CCR5的表达来区分。表型分析表明了分化的分级模式，未成熟的CD4 + CD8-CCR5-细胞进入了中间CD4 + CD8-CCR5 +阶段，该阶段的分化程度不及CD4-CD8-和CD4-CD8 +子集，后者均表达CCR5。这种解释得到了功能性数据的支持，这些功能性数据包括克隆形成潜能和细胞因子分泌特征以及T细胞受体（TCR）切除圆环分析。此外，相应的TCR曲目的常规和高通量测序证明了个体内显着的克隆型重叠，特别是在差异更大的CD4- CD8-和CD4- CD8 +亚集之间。总体而言，这些结果绘制了人类CD1d限制的NKT细胞胸腺后景观的线性分化途径。