ArticleThe Journal of experimental medicine2021
A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS.
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Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Impaired regulation by purinergic signaling axis contributes to CD8+ T cell dysregulation in STAT3 gain of function.JCI insight · 2026Article
- cFLIP suppresses caspase-1- and MLKL-independent perinatal lethality driven by auto-processing impaired caspase-8 D387A.Cell death and differentiation · 2026Article
- FAS-controlled T cells drive lymphoproliferation through glycolysis without effector differentiation.Journal of human immunity · 2026Article
- Double negative T cells decline in inflammatory reproductive dysfunction.Scientific reports · 2026Article
- The Fas-FasL system: from apoptosis regulator to therapeutic target in autoimmunity, cancer, and transplantation.Immunologic research · 2026Review
- Remodeling of the immune microenvironment is linked to adverse outcome in pediatric T cell acute lymphoblastic leukemia.Nature communications · 2025Article
- Opinion: Why paediatric rheumatologists need to understand inborn errors of immunity.Frontiers in pediatrics · 2025Article
- Pseudo-spectral angle mapping for pixel and cell classification in highly multiplexed immunofluorescence images.Journal of medical imaging (Bellingham, Wash.) · 2024Article
- Genetic Testing in Patients with Autoimmune Lymphoproliferative Syndrome: Experience of 802 Patients at Cincinnati Children's Hospital Medical Center.Journal of clinical immunology · 2024Article
- Helper T cell immunity in humans with inherited CD4 deficiency.The Journal of experimental medicine · 2024Article
- Pseudo-spectral angle mapping for automated pixel-level analysis of highly multiplexed tissue image data.bioRxiv : the preprint server for biology · 2024Article
- Autoimmune lymphoproliferative immunodeficiencies (ALPIDs): A proposed approach to redefining ALPS and other lymphoproliferative immune disorders.The Journal of allergy and clinical immunology · 2024Review
- Autoimmune lymphoproliferative immunodeficiencies (ALPID) in childhood: breakdown of immune homeostasis and immune dysregulation.Molecular and cellular pediatrics · 2023Review
- Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.The Journal of allergy and clinical immunology · 2023Article
- Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis.The Journal of experimental medicine · 2023Article
- BMP-6 promotes type 2 immune response during enhancement of rat mandibular bone defect healing.Frontiers in immunology · 2023Article
- T Cells in Multisystem Inflammatory Syndrome in Children (MIS-C) Have a Predominant CD4+ T Helper Response to SARS-CoV-2 Peptides and Numerous Virus-Specific CD4- CD8- Double-Negative T Cells.International journal of molecular sciences · 2022Article
- Expansion of Double-Negative T Cells in Patients before Liver Transplantation Correlates with Post-Transplant Infections.Journal of clinical medicine · 2022Article
- T Cell Homeostatic Proliferation Promotes a Redox State That Drives Metabolic and Epigenetic Upregulation of Inflammatory Pathways in Lupus.Antioxidants & redox signaling · 2022Review
- ALPS, FAS, and beyond: from inborn errors of immunity to acquired immunodeficiencies.Annals of hematology · 2022Review
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Authors and funding
49 authors at 17 institutions in 6 countries.
Maria Elena MaccariInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Sebastian FuchsRoche Pharma Research and Early Development, Immunology, Infectious Diseases and Ophthalmology (I2O) Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.
Patrick KuryInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Geoffroy AndrieuxInstitute of Medical Bioinformatics and Systems Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Simon VölklDepartment of Internal Medicine 5-Hematology/Oncology, University of Erlangen, Erlangen, Germany.
Bertram BengschDepartment of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Myriam Ricarda LorenzInstitute for Transfusion Medicine, University of Ulm, Ulm, Germany.
Maximilian HeegInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Jan RohrInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Sabine JägleInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Carla N CastroInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Miriam GroßInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Ursula WarthorstInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Christoph KönigInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Ilka FuchsInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Carsten SpeckmannInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Julian ThalhammerInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Friedrich G KappDivision of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Markus G SeidelDivision of Pediatric Hematology-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria.
Gregor DückersHelios Kliniken Krefeld, Children's Hospital, Krefeld, Germany.
Stefan SchönbergerUniversity of Bonn, Department of Paediatric Haematology and Oncology, University Children's Hospital Bonn, Germany.
Catharina SchützDepartment of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Marita FührerInstitute for Transfusion Medicine, University of Ulm, Ulm, Germany.
Robin KobbeFirst Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Dirk HolzingerDepartment of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany.
Christian KlemannDepartment of Pediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.
Petr SmisekDepartment of Pediatric Hematology and Oncology, University Hospital Motol and Second Faculty of Medicine, Charles University, Prague, Czech Republic.
Stephen OwensGreat North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Gerd HorneffDepartment of General Paediatrics, Clinic Sankt Augustin, Sankt Augustin, Germany.
Reinhard KolbDepartment of General Paediatrics, Clinic Oldenburg, Oldenburg, Germany.
Nora Naumann-BartschDepartment of Pediatrics, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Maurizio MianoHaematology Unit, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Giannina Gaslini, Genoa, Italy.
Julian StaniekFaculty of Biology, University of Freiburg, Freiburg, Germany.
Marta RizziInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Tomas KalinaChildhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, Second Medical School, Charles University and University Hospital Motol, Prague, Czech Republic.
Pascal SchneiderDepartment of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Anika ErxlebenBioinformatics, Institute for Computer Science, Faculty of Engineering, University of Freiburg, Germany.
Rolf BackofenBioinformatics, Institute for Computer Science, Faculty of Engineering, University of Freiburg, Germany.
Arif EkiciInstitute of Human Genetics, University of Erlangen, Erlangen, Germany.
Charlotte M NiemeyerDivision of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Klaus WarnatzInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Bodo GrimbacherInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Hermann EibelInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Andreas MackensenDepartment of Internal Medicine 5-Hematology/Oncology, University of Erlangen, Erlangen, Germany.
Andreas Philipp FreiRoche Pharma Research and Early Development, Immunology, Infectious Diseases and Ophthalmology (I2O) Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.
Klaus SchwarzInstitute for Transfusion Medicine, University of Ulm, Ulm, Germany.
Melanie BoerriesInstitute of Medical Bioinformatics and Systems Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Stephan EhlInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Anne Rensing-EhlInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
University of Freiburg · DEFriedrich-Alexander-Universität Erlangen-Nürnberg · DEUniversität Ulm · DECharles University · CZRoche (Switzerland) · CHAsklepios Klinik Sankt Augustin · DEHelios Klinikum Krefeld · DEIstituto Giannina Gaslini · ITKlinikum Oldenburg · DEMedical University of Graz · ATMedizinische Hochschule Hannover · DENewcastle upon Tyne Hospitals NHS Foundation Trust · GBUniversität Hamburg · DEUniversity Hospital Carl Gustav Carus · DEUniversity of Bonn · DEUniversity of Duisburg-Essen · DEUniversity of Lausanne · CH
Funding
No grant is acknowledged in the PubMed record.
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.
Indexed as
AdolescentADP-ribosyl Cyclase 1AdultAgedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesChildChild, Preschoolfas ReceptorFemaleHumansInfantInfant, NewbornLeukocyte Common AntigensLymphocyte ActivationLymphoproliferative DisordersADP-ribosyl Cyclase 1fas ReceptorLeukocyte Common Antigens
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