Two subsets of regulatory CD8+ T cells with differential transcriptome revealed by single cell analysis

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-09-08 DOI:10.1016/j.isci.2025.113512

Céline Sérazin , Lisa Dugast , Léa Flippe , Mathias Streitz , Désirée-Jacqueline Wendering , Stephan Schlickeiser , Frederik Heinrich , Pawel Durek , Gabriela Maria Guerra , Katrin Lehmann , Mir-Farzin Mashreghi , Harald Wajant , Hans Dieter Volk , Ignacio Anegon , Laurent David , Séverine Bézie , Carole Guillonneau

{"title":"Two subsets of regulatory CD8+ T cells with differential transcriptome revealed by single cell analysis","authors":"Céline Sérazin , Lisa Dugast , Léa Flippe , Mathias Streitz , Désirée-Jacqueline Wendering , Stephan Schlickeiser , Frederik Heinrich , Pawel Durek , Gabriela Maria Guerra , Katrin Lehmann , Mir-Farzin Mashreghi , Harald Wajant , Hans Dieter Volk , Ignacio Anegon , Laurent David , Séverine Bézie , Carole Guillonneau","doi":"10.1016/j.isci.2025.113512","DOIUrl":null,"url":null,"abstract":"<div><div>Although CD8<sup>+</sup> regulatory T cells (Tregs) were described in the 1970’s, they remain poorly defined compared to CD4<sup>+</sup> Tregs. Their phenotypic heterogeneity and lack of consensus markers have hindered mechanistic studies and slowed clinical development despite their therapeutic potential. In this study, we performed single-cell RNA sequencing coupled with CITE-seq and TCR-seq on peripheral blood CD8<sup>+</sup> T cells from four healthy donors, including the CD45RC marker to distinguish pro-inflammatory from pro-regulatory subsets. We analyzed ∼7000 freshly isolated, non-stimulated CD8<sup>+</sup> T cells and identified two distincts CD8<sup>+</sup> Tregs subsets, defined by HELIOS or TNFR2 expression, with unique transcriptional and surface marker profiles. Functional assays revealed potent suppressive capacity of the TNFR2<sup>+</sup>CD29<sup>low</sup>CD45RC<sup>low/-</sup> subset. These findings were independently validated using a publicly available single-cell dataset from four additional individuals. This work provides the most comprehensive profiling of human CD8<sup>+</sup> Tregs to date and supports their translation to clinical application.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113512"},"PeriodicalIF":4.1000,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"iScience","FirstCategoryId":"103","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589004225017730","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Although CD8⁺ regulatory T cells (Tregs) were described in the 1970’s, they remain poorly defined compared to CD4⁺ Tregs. Their phenotypic heterogeneity and lack of consensus markers have hindered mechanistic studies and slowed clinical development despite their therapeutic potential. In this study, we performed single-cell RNA sequencing coupled with CITE-seq and TCR-seq on peripheral blood CD8⁺ T cells from four healthy donors, including the CD45RC marker to distinguish pro-inflammatory from pro-regulatory subsets. We analyzed ∼7000 freshly isolated, non-stimulated CD8⁺ T cells and identified two distincts CD8⁺ Tregs subsets, defined by HELIOS or TNFR2 expression, with unique transcriptional and surface marker profiles. Functional assays revealed potent suppressive capacity of the TNFR2⁺CD29^lowCD45RC^low/- subset. These findings were independently validated using a publicly available single-cell dataset from four additional individuals. This work provides the most comprehensive profiling of human CD8⁺ Tregs to date and supports their translation to clinical application.

Abstract Image

查看原文本刊更多论文

单细胞分析揭示了两个具有差异转录组的调节性CD8+ T细胞亚群

尽管CD8+调节性T细胞（treg）在20世纪70年代被描述，但与CD4+ treg相比，它们仍然定义不清。它们的表型异质性和缺乏共识的标记物阻碍了机制研究，减缓了临床发展，尽管它们具有治疗潜力。在这项研究中，我们对来自四个健康供者的外周血CD8+ T细胞进行了单细胞RNA测序，结合CITE-seq和TCR-seq，包括CD45RC标记物，以区分促炎症亚群和促调节亚群。我们分析了约7000个新分离的、未受刺激的CD8+ T细胞，并鉴定出两个不同的CD8+ Tregs亚群，由HELIOS或TNFR2表达定义，具有独特的转录和表面标记谱。功能分析显示TNFR2+ cd29lowcd45rlow /-亚群具有强大的抑制能力。这些发现是使用另外四个人的公开单细胞数据集独立验证的。这项工作提供了迄今为止最全面的人类CD8+ treg图谱，并支持它们转化为临床应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.