The effector program of human CD8 T cells supports tissue remodeling-Reference-Cited by-同舟云学术

The effector program of human CD8 T cells supports tissue remodeling

Published:2024-01-16 Issue:2 Volume:221 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Delacher Michael¹²³⁴^ORCID,Schmidleithner Lisa¹²^ORCID,Simon Malte¹⁵⁶^ORCID,Stüve Philipp¹²^ORCID,Sanderink Lieke¹²^ORCID,Hotz-Wagenblatt Agnes⁷^ORCID,Wuttke Marina¹²^ORCID,Schambeck Kathrin¹²^ORCID,Ruhland Brigitte¹²^ORCID,Hofmann Veronika¹²^ORCID,Bittner Sebastian¹²^ORCID,Ritter Uwe¹²^ORCID,Pant Asmita¹²^ORCID,Helbich Sara Salome³⁴^ORCID,Voss Morten³⁴^ORCID,Lemmermann Niels A.⁴⁸⁹^ORCID,Bessiri-Schake Lisa³⁴^ORCID,Bohn Toszka³⁴^ORCID,Eigenberger Andreas¹⁰^ORCID,Menevse Ayse Nur¹¹¹^ORCID,Gebhard Claudia¹^ORCID,Strieder Nicholas¹^ORCID,Abken Hinrich¹¹²^ORCID,Rehli Michael¹¹³^ORCID,Huehn Jochen¹⁴¹⁵¹⁶^ORCID,Beckhove Philipp¹¹¹¹³^ORCID,Hehlgans Thomas¹²^ORCID,Junger Henrik¹⁷^ORCID,Geissler Edward K.¹⁷^ORCID,Prantl Lukas¹⁰^ORCID,Werner Jens M.¹⁷^ORCID,Schmidl Christian¹^ORCID,Brors Benedikt⁵¹⁸⁶¹⁹²⁰^ORCID,Imbusch Charles D.³⁴⁶^ORCID,Feuerer Markus¹²^ORCID

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

Subject

Immunology,Immunology and Allergy

Link

https://rupress.org/jem/article-pdf/doi/10.1084/jem.20230488/1922884/jem_20230488.pdf

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