Antigen presentation safeguards the integrity of the hematopoietic stem cell pool.

Autor:	Hernández-Malmierca P; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany., Vonficht D; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany., Schnell A; Evergrande Center for Immunologic Diseases, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Uckelmann HJ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Boston, MA, USA; Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Bollhagen A; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany., Mahmoud MAA; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany., Landua SL; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany., van der Salm E; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany., Trautmann CL; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany., Raffel S; Department of Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany., Grünschläger F; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany., Lutz R; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany; Department of Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany., Ghosh M; Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany., Renders S; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany; Department of Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany., Correia N; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany., Donato E; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany., Dixon KO; Evergrande Center for Immunologic Diseases, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Hirche C; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Inflammatory Stress in Stem Cells, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Andresen C; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany., Robens C; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany., Werner PS; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Inflammatory Stress in Stem Cells, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Boch T; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany; Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany; Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Eisel D; Research Group GMP & T Cell Therapy, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany., Osen W; Research Group GMP & T Cell Therapy, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany., Pilz F; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Inflammatory Stress in Stem Cells, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Przybylla A; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany., Klein C; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany., Buchholz F; Medical Faculty, University Hospital Carl Gustav Carus, NCT/UCC Section Medical Systems Biology, TU Dresden, Dresden, Germany., Milsom MD; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Experimental Hematology, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Essers MAG; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Inflammatory Stress in Stem Cells, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Eichmüller SB; Research Group GMP & T Cell Therapy, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany., Hofmann WK; Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany; Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Nowak D; Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany; Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Hübschmann D; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Computational Oncology, Molecular Precision Oncology Program, National Center for Tumor Diseases (NCT) Heidelberg and Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany., Hundemer M; Department of Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany., Thiede C; German Cancer Consortium (DKTK), Heidelberg, Germany; Medical Department 1, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany., Bullinger L; German Cancer Consortium (DKTK), Heidelberg, Germany; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Cancer Immunology, Berlin, Germany., Müller-Tidow C; Department of Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany; Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, University of Heidelberg, Heidelberg, Germany., Armstrong SA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Hematology/Oncology, Boston, MA, USA; Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Trumpp A; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: a.trumpp@dkfz.de., Kuchroo VK; Evergrande Center for Immunologic Diseases, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: vkuchroo@evergrande.hms.harvard.edu., Haas S; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Cancer Immunology, Berlin, Germany; Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. Electronic address: simon.haas@bih-charite.de.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2022 May 05; Vol. 29 (5), pp. 760-775.e10.
DOI:	10.1016/j.stem.2022.04.007
Abstrakt:	Hematopoietic stem and progenitor cells (HSPCs) are responsible for the production of blood and immune cells. Throughout life, HSPCs acquire oncogenic aberrations that can cause hematological cancers. Although molecular programs maintaining stem cell integrity have been identified, safety mechanisms eliminating malignant HSPCs from the stem cell pool remain poorly characterized. Here, we show that HSPCs constitutively present antigens via major histocompatibility complex class II. The presentation of immunogenic antigens, as occurring during malignant transformation, triggers bidirectional interactions between HSPCs and antigen-specific CD4 + T cells, causing stem cell proliferation, differentiation, and specific exhaustion of aberrant HSPCs. This immunosurveillance mechanism effectively eliminates transformed HSPCs from the hematopoietic system, thereby preventing leukemia onset. Together, our data reveal a bidirectional interaction between HSPCs and CD4 + T cells, demonstrating that HSPCs are not only passive receivers of immunological signals but also actively engage in adaptive immune responses to safeguard the integrity of the stem cell pool. Competing Interests: Declaration of interests V.K.K. is a cofounder, has ownership interest, and is on the SAB of Celsius Therapeutics and Tizona Therapeutics. (Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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