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Two subsets of stem-like CD8 + memory T cell progenitors with distinct fate commitments in humans
Nature Immunology ( IF 30.5 ) Pub Date : 2020-10-12 , DOI: 10.1038/s41590-020-0791-5
Giovanni Galletti 1 , Gabriele De Simone 1 , Emilia M C Mazza 1 , Simone Puccio 1 , Claudia Mezzanotte 2 , Timothy M Bi 3 , Alexey N Davydov 4 , Maria Metsger 4 , Eloise Scamardella 1 , Giorgia Alvisi 1 , Federica De Paoli 1 , Veronica Zanon 1 , Alice Scarpa 1 , Barbara Camisa 2 , Federico S Colombo 5 , Achille Anselmo 5 , Clelia Peano 6, 7 , Sara Polletti 8 , Domenico Mavilio 9, 10 , Luca Gattinoni 11, 12, 13 , Shannon K Boi 14 , Benjamin A Youngblood 14 , Rhiannon E Jones 15 , Duncan M Baird 15 , Emma Gostick 16 , Sian Llewellyn-Lacey 16 , Kristin Ladell 16 , David A Price 16, 17 , Dmitriy M Chudakov 18, 19, 20 , Evan W Newell 3 , Monica Casucci 2 , Enrico Lugli 1, 5
Affiliation  

T cell memory relies on the generation of antigen-specific progenitors with stem-like properties. However, the identity of these progenitors has remained unclear, precluding a full understanding of the differentiation trajectories that underpin the heterogeneity of antigen-experienced T cells. We used a systematic approach guided by single-cell RNA-sequencing data to map the organizational structure of the human CD8+ memory T cell pool under physiological conditions. We identified two previously unrecognized subsets of clonally, epigenetically, functionally, phenotypically and transcriptionally distinct stem-like CD8+ memory T cells. Progenitors lacking the inhibitory receptors programmed death-1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were committed to a functional lineage, whereas progenitors expressing PD-1 and TIGIT were committed to a dysfunctional, exhausted-like lineage. Collectively, these data reveal the existence of parallel differentiation programs in the human CD8+ memory T cell pool, with potentially broad implications for the development of immunotherapies and vaccines.



中文翻译:

干细胞样 CD8 + 记忆 T 细胞祖细胞的两个亚群在人类中具有不同的命运承诺

T 细胞记忆依赖于具有干细胞特性的抗原特异性祖细胞的产生。然而,这些祖细胞的身份仍不清楚,无法全面了解支持抗原经历的 T 细胞异质性的分化轨迹。我们使用以单细胞 RNA 测序数据为指导的系统方法来绘制生理条件下人类 CD8 +记忆 T 细胞池的组织结构。我们鉴定了两个以前未被识别的克隆、表观遗传、功能、表型和转录上不同的干细胞样 CD8 +亚群记忆T细胞。缺乏抑制性受体程序性死亡-1 (PD-1) 和具有 Ig 和 ITIM 结构域的 T 细胞免疫受体 (TIGIT) 的祖细胞致力于功能谱系,而表达 PD-1 和 TIGIT 的祖细胞致力于功能失调、疲惫样血统。总的来说,这些数据揭示了人类 CD8 +记忆 T 细胞库中存在平行分化程序,这对免疫疗法和疫苗的开发具有潜在的广泛影响。

更新日期:2020-10-12
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