意大利IRCCS-基金会Enrico Lugli及其研究团队发现，在人体中两个干细胞样CD8⁺记忆T细胞祖细胞亚群具有不同的细胞命运。这一研究成果发表在2020年10月12日出版的国际学术期刊《自然-免疫学》上。

利用基于单细胞RNA测序数据为依托的系统方法，研究人员绘制了生理条件下人CD8⁺记忆T细胞群的组织结构图。研究人员揭示了两个之前未知的克隆、表观遗传、功能、表型和转录不同的干细胞样CD8⁺记忆T细胞亚群。缺乏抑制性受体-程序性死亡-1（PD-1）和具有Ig和ITIM结构域（TIGIT）的T细胞祖细胞亚群主要分化为功能谱系，而表达PD-1和TIGIT的祖细胞则分化为功能障碍、衰竭样谱系。

总的来说，这些数据证明了在人CD8⁺记忆T细胞库中存在平行的分化程序，这对免疫疗法和疫苗开发具有潜在的影响。

据介绍，T细胞记忆依赖于具有干细胞样特性抗原特异性祖细胞的产生。然而，这些祖细胞的来源仍然不清楚，这阻碍对T细胞受到不同抗原刺激时异质性分化轨迹的充分理解。

附：英文原文

Title: Two subsets of stem-like CD8 + memory T cell progenitors with distinct fate commitments in humans

Author: Giovanni Galletti, Gabriele De Simone, Emilia M. C. Mazza, Simone Puccio, Claudia Mezzanotte, Timothy M. Bi, Alexey N. Davydov, Maria Metsger, Eloise Scamardella, Giorgia Alvisi, Federica De Paoli, Veronica Zanon, Alice Scarpa, Barbara Camisa, Federico S. Colombo, Achille Anselmo, Clelia Peano, Sara Polletti, Domenico Mavilio, Luca Gattinoni, Shannon K. Boi, Benjamin A. Youngblood, Rhiannon E. Jones, Duncan M. Baird, Emma Gostick, Sian Llewellyn-Lacey, Kristin Ladell, David A. Price, Dmitriy M. Chudakov, Evan W. Newell, Monica Casucci, Enrico Lugli

Issue&Volume: 2020-10-12

Abstract: 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. The identity of stem-cell memory progenitor cells has been unclear. Lugli and colleagues use high-dimensional approaches to identify two new progenitor populations of human T cells—one giving rise to a functional lineage, the other to an exhausted-like one.

DOI: 10.1038/s41590-020-0791-5

Source: https://www.nature.com/articles/s41590-020-0791-5