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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Characterization of subsets of CD4~+ memory T cells reveals early branched pathways of T cell differentiation in humans
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Characterization of subsets of CD4~+ memory T cells reveals early branched pathways of T cell differentiation in humans

机译：CD4〜+记忆T细胞子集的表征揭示了人类T细胞分化的早期分支途径

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The pathways for differentiation of human CD4~+ T cells into functionally distinct subsets of memory cells in vivo are unknown. The identification of these subsets and pathways has clear implications for the design of vaccines and immune-targeted therapies. Here, we show that populations of apparently naieve CD4~+ T cells express the chemokine receptors CXCR3 or CCR4 and demonstrate patterns of gene expression and functional responses characteristic of memory cells. The proliferation history and T cell receptor repertoire of these chemokine-receptor~+ cells suggest that they are very early memory CD4~+ T cells that have "rested down" before acquiring the phenotypes described for "central" or "effector" memory T cells. In addition, the chemokine-receptor~+ "naieve" populations contain Th1 and Th2 cells, respectively, demonstrating that Th1/Th2 differentiation can occur very early in vivo in the absence of markers conventionally associated with memory cells. We localized ligands for CXCR3 and CCR4 to separate foci in T cell zones of tonsil, suggesting that the chemokine-receptor~+ subsets may be recruited and contribute to segregated, polarized micro-environments within lymphoid organs. Importantly, our data suggest that CD4~+ T cells do not differentiate according to a simple schema from naieve → CD45RO~+ noneffector/central memory → effector/effector memory cells. Rather, developmental pathways branch early on to yield effector/memory populations that are highly heterogeneous and multifunctional and have the potential to become stable resting cells.
机译：体内人类CD4〜+ T细胞分化为功能不同的记忆细胞的途径尚不清楚。这些子集和途径的鉴定对疫苗和免疫靶向疗法的设计具有明显的意义。在这里，我们显示了看起来很幼稚的CD4〜+ T细胞群体表达趋化因子受体CXCR3或CCR4，并证明了基因表达的模式和记忆细胞特有的功能性反应。这些趋化因子受体〜+细胞的增殖史和T细胞受体库表明，它们是非常早期的记忆CD4〜+ T细胞，在获得描述为“中央”或“效应”记忆T细胞的表型之前已经“静止”。 。另外，趋化因子-受体“天然”群体分别含有Th1和Th2细胞，这表明在没有通常与记忆细胞相关的标志物的情况下，Th1 / Th2分化可以在体内很早地发生。我们将CXCR3和CCR4的配体定位在扁桃体的T细胞区域中，以分离病灶，这表明趋化因子受体〜+子集可能被募集并有助于淋巴器官内分离的，极化的微环境。重要的是，我们的数据表明，CD4〜+ T细胞没有按照简单的模式与幼稚→CD45RO〜+非效应细胞/中央记忆→效应子/效应细胞分化。而是，发育途径会尽早分支到产生高度异质和多功能的效应子/记忆种群，并有可能成为稳定的静止细胞。

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