A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS-Reference-Cited by-同舟云学术

A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS

Published:2020-11-10 Issue:2 Volume:218 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Maccari Maria Elena¹²^ORCID,Fuchs Sebastian³^ORCID,Kury Patrick¹⁴^ORCID,Andrieux Geoffroy⁵⁶^ORCID,Völkl Simon⁷^ORCID,Bengsch Bertram⁸⁹¹⁰^ORCID,Lorenz Myriam Ricarda¹¹¹²^ORCID,Heeg Maximilian¹²^ORCID,Rohr Jan¹²^ORCID,Jägle Sabine¹^ORCID,Castro Carla N.¹^ORCID,Groß Miriam¹⁴^ORCID,Warthorst Ursula¹,König Christoph¹⁴^ORCID,Fuchs Ilka¹^ORCID,Speckmann Carsten¹²^ORCID,Thalhammer Julian¹²^ORCID,Kapp Friedrich G.²^ORCID,Seidel Markus G.¹³^ORCID,Dückers Gregor¹⁴^ORCID,Schönberger Stefan¹⁵^ORCID,Schütz Catharina¹⁶^ORCID,Führer Marita¹¹¹²^ORCID,Kobbe Robin¹⁷^ORCID,Holzinger Dirk¹⁸^ORCID,Klemann Christian¹⁹^ORCID,Smisek Petr²⁰^ORCID,Owens Stephen²¹²²^ORCID,Horneff Gerd²³²⁴^ORCID,Kolb Reinhard²⁵^ORCID,Naumann-Bartsch Nora²⁶^ORCID,Miano Maurizio²⁷^ORCID,Staniek Julian⁴²⁸^ORCID,Rizzi Marta¹²⁸^ORCID,Kalina Tomas²⁹^ORCID,Schneider Pascal³⁰^ORCID,Erxleben Anika³¹^ORCID,Backofen Rolf³¹^ORCID,Ekici Arif³²^ORCID,Niemeyer Charlotte M.²^ORCID,Warnatz Klaus¹^ORCID,Grimbacher Bodo¹⁹³³³⁴^ORCID,Eibel Hermann¹^ORCID,Mackensen Andreas⁷^ORCID,Frei Andreas Philipp³^ORCID,Schwarz Klaus¹¹¹²,Boerries Melanie⁵⁶^ORCID,Ehl Stephan¹²⁹^ORCID,Rensing-Ehl Anne¹^ORCID

Affiliation:

1. Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2. Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

3. Roche Pharma Research and Early Development, Immunology, Infectious Diseases and Ophthalmology (I2O) Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland

4. Faculty of Biology, University of Freiburg, Freiburg, Germany

5. Institute of Medical Bioinformatics and Systems Medicine, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

6. German Cancer Consortium, Freiburg, and German Cancer Research Center, Heidelberg, Germany

7. Department of Internal Medicine 5–Hematology/Oncology, University of Erlangen, Erlangen, Germany

8. Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

9. Center for Integrative Biological Signaling Studies, Albert-Ludwigs University, Freiburg, Germany

10. Bioss Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany

11. Institute for Transfusion Medicine, University of Ulm, Ulm, Germany

12. Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Service Baden-Wuerttemberg–Hessen, Ulm, Germany

13. Division of Pediatric Hematology-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria

14. Helios Kliniken Krefeld, Children’s Hospital, Krefeld, Germany

15. University of Bonn, Department of Paediatric Haematology and Oncology, University Children's Hospital Bonn, Germany

16. Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

17. First Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

18. Department of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany

19. Department of Pediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany

20. Department of Pediatric Hematology and Oncology, University Hospital Motol and Second Faculty of Medicine, Charles University, Prague, Czech Republic

21. Great North Children’s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

22. Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK

23. Department of General Paediatrics, Clinic Sankt Augustin, Sankt Augustin, Germany

24. Department of Pediatric and Adolescent Medicine, University Hospital of Cologne, Cologne, Germany

25. Department of General Paediatrics, Clinic Oldenburg, Oldenburg, Germany

26. Department of Pediatrics, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany

27. Haematology Unit, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Giannina Gaslini, Genoa, Italy

28. Department of Rheumatology and Clinical Immunology, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

29. Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, Second Medical School, Charles University and University Hospital Motol, Prague, Czech Republic

30. Department of Biochemistry, University of Lausanne, Epalinges, Switzerland

31. Bioinformatics, Institute for Computer Science, Faculty of Engineering, University of Freiburg, Germany

32. Institute of Human Genetics, University of Erlangen, Erlangen, Germany

33. German Center for Infection Research, Satellite Center, Freiburg, Germany

34. Resolving Infection Susceptibility Cluster of Excellence 2155, Hanover Medical School, Satellite Center, Freiburg, Germany

Abstract

The identification and characterization of rare immune cell populations in humans can be facilitated by their growth advantage in the context of specific genetic diseases. Here, we use autoimmune lymphoproliferative syndrome to identify a population of FAS-controlled TCRαβ+ T cells. They include CD4+, CD8+, and double-negative T cells and can be defined by a CD38+CD45RA+T-BET− expression pattern. These unconventional T cells are present in healthy individuals, are generated before birth, are enriched in lymphoid tissue, and do not expand during acute viral infection. They are characterized by a unique molecular signature that is unambiguously different from other known T cell differentiation subsets and independent of CD4 or CD8 expression. Functionally, FAS-controlled T cells represent highly proliferative, noncytotoxic T cells with an IL-10 cytokine bias. Mechanistically, regulation of this physiological population is mediated by FAS and CTLA4 signaling, and its survival is enhanced by mTOR and STAT3 signals. Genetic alterations in these pathways result in expansion of FAS-controlled T cells, which can cause significant lymphoproliferative disease.

Funder

Wilhelm Sander Stiftung

Federal Ministry of Education and Research

CoNfirm

German Research Foundation

University of Freiburg

Else–Kröner–Fresenius–Stiftung

Berta-Ottenstein-Program for Clinician Scientists

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy