The effector program of human CD8 T cells supports tissue remodeling

Author:

Delacher Michael1234ORCID,Schmidleithner Lisa12ORCID,Simon Malte156ORCID,Stüve Philipp12ORCID,Sanderink Lieke12ORCID,Hotz-Wagenblatt Agnes7ORCID,Wuttke Marina12ORCID,Schambeck Kathrin12ORCID,Ruhland Brigitte12ORCID,Hofmann Veronika12ORCID,Bittner Sebastian12ORCID,Ritter Uwe12ORCID,Pant Asmita12ORCID,Helbich Sara Salome34ORCID,Voss Morten34ORCID,Lemmermann Niels A.489ORCID,Bessiri-Schake Lisa34ORCID,Bohn Toszka34ORCID,Eigenberger Andreas10ORCID,Menevse Ayse Nur111ORCID,Gebhard Claudia1ORCID,Strieder Nicholas1ORCID,Abken Hinrich112ORCID,Rehli Michael113ORCID,Huehn Jochen141516ORCID,Beckhove Philipp11113ORCID,Hehlgans Thomas12ORCID,Junger Henrik17ORCID,Geissler Edward K.17ORCID,Prantl Lukas10ORCID,Werner Jens M.17ORCID,Schmidl Christian1ORCID,Brors Benedikt51861920ORCID,Imbusch Charles D.346ORCID,Feuerer Markus12ORCID

Affiliation:

1. Leibniz Institute for Immunotherapy 1 , Regensburg, Germany

2. Chair for Immunology, University Regensburg 2 , Regensburg, Germany

3. Institute of Immunology, University Medical Center Mainz 5 , Mainz, Germany

4. Research Center for Immunotherapy, University Medical Center Mainz 6 , Mainz, Germany

5. Faculty of Biosciences, Heidelberg University 8 , Heidelberg, Germany

6. German Cancer Research Center 10 Division of Applied Bioinformatics, , Heidelberg, Germany

7. Core Facility Omics IT and Data Management, German Cancer Research Center 11 , Heidelberg, Germany

8. Institute of Virology, University Medical Center Mainz 7 , Mainz, Germany

9. Institute of Virology, University of Bonn 12 , Bonn, Germany

10. University Hospital Regensburg 13 Department of Plastic, Hand- and Reconstructive Surgery, , Regensburg, Germany

11. Chair for Interventional Immunology, University Regensburg 3 , Regensburg, Germany

12. Chair for Genetic Immunotherapy, University Regensburg 4 , Regensburg, Germany

13. University Hospital Regensburg 14 Department of Internal Medicine III, , Regensburg, Germany

14. Helmholtz Centre for Infection Research 15 Department of Experimental Immunology, , Braunschweig, Germany

15. Hannover Medical School 16 , Hannover, Germany

16. RESIST, Cluster of Excellence 2155, Hannover Medical School 17 , Hannover, Germany

17. University Hospital Regensburg 18 Department of Surgery, , Regensburg, Germany

18. Faculty of Medicine Heidelberg, Heidelberg University 9 , Heidelberg, Germany

19. National Center for Tumor Diseases 19 , Heidelberg, Germany

20. German Cancer Consortium, German Cancer Research Center 20 , Heidelberg, Germany

Abstract

CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a tissue regeneration program is poorly understood. Here, antigen-specific assay systems revealed that human CD8 T cells not only mediated cytotoxicity but also promoted tissue remodeling. Activated CD8 T cells could produce the epidermal growth factor receptor (EGFR)-ligand amphiregulin (AREG) and sensitize epithelial cells for enhanced regeneration potential. Blocking the EGFR or the effector cytokines IFN-γ and TNF could inhibit tissue remodeling. This regenerative program enhanced tumor spheroid and stem cell–mediated organoid growth. Using single-cell gene expression analysis, we identified an AREG+, tissue-resident CD8 T cell population in skin and adipose tissue from patients undergoing abdominal wall or abdominoplasty surgery. These tissue-resident CD8 T cells showed a strong TCR clonal relation to blood PD1+TIGIT+ CD8 T cells with tissue remodeling abilities. These findings may help to understand the complex CD8 biology in tumors and could become relevant for the design of therapeutic T cell products.

Funder

European Research Council

Deutsche Forschungsgemeinschaft

Else-Kröner-Fresenius-Stiftung

Publisher

Rockefeller University Press

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3