The gene expression profile of phosphoantigen-specific human ?d T lymphocytes is a blend of aß T-cell and NK-cell signatures

The gene expression profile of phosphoantigen-specific human ?d T lymphocytes is a blend of aß T-cell and NK-cell signatures
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DOI:
10.1002/eji.201141870
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发表时间:
2012-01-01
影响因子:
5.4
通讯作者:
Fournie, Jean-Jacques
Fournie, Jean-Jacques
中科院分区:
医学3区
文献类型:
--
作者:
Pont, Frederic;Familiades, Julien;Fournie, Jean-Jacques

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全球转录技术已经彻底改变了对淋巴样细胞群体的研究,但是,尽管这些细胞具有巨大的治疗潜力,但这些方法对针对磷抗原的人类伽马三角洲T淋巴细胞的特征仍然远远不够深入。在这里,我们分析了从健康个体分离的循环TCRVγ(+)γ-Delta T细胞的转录组,以及它们与其他淋巴细胞亚群的转录组的关系。我们报道了磷酸化抗原特异性的TCRVγ(+)γ-Delta T细胞的基因特征是来自βT细胞和NK细胞的混合,具有比βT细胞更多的NK细胞基因和比NK细胞更多的T细胞基因。磷酸抗原刺激的TCRVγ(+)γDelta T细胞的表达谱概括了它们的即时生理功能:Th1细胞因子、趋化因子和细胞毒活性反映了它们在以后的时间点上的高有丝分裂活性,而不是抗原提呈功能。最后,这些特征使伽马三角洲T细胞的转录组,无论是静止的还是克隆性扩张的,明显有别于NK/T或伽马三角洲亚型的外周T细胞淋巴瘤。
Global transcriptional technologies have revolutionised the study of lymphoid cell populations, but human gamma delta T lymphocytes specific for phosphoantigens remain far less deeply characterised by these methods despite the great therapeutic potential of these cells. Here we analyse the transcriptome of circulating TCRV gamma(+) gamma delta T cells isolated from healthy individuals, and their relation with those from other lymphoid cell subsets. We report that the gene signature of phosphoantigen-specific TCRV gamma(+) gamma delta T cells is a hybrid of those from a beta T and NK cells, with more NK-cell genes than a beta T cells have and more T-cell genes than NK cells. The expression profile of TCRV gamma(+) gamma delta T cells stimulated with phosphoantigen recapitulates their immediate physiological functions: Th1 cytokine, chemokine and cytotoxic activities reflect their high mitotic activity at later time points and do not indicate antigen-presenting functions. Finally, such hallmarks make the transcriptome of gamma delta T cells, whether resting or clonally expanding, clearly distinctive from that of NK/T or peripheral T-cell lymphomas of the gamma delta subtype.