Single-cell clonal tracking of persistent T-cells in allogeneic hematopoietic stem cell transplantation.

Autor: Obermayer B; Core Unit Bioinformatics (CUBI), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany., Keilholz L; Department of Hematology, Oncology, and Tumor Immunology, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany., Conrad T; Core Unit Genomics, Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany.; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany., Frentsch M; Department of Hematology, Oncology, and Tumor Immunology, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany., Blau IW; Department of Hematology, Oncology, and Tumor Immunology, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Vuong L; Department of Hematology, Oncology, and Tumor Immunology, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; Stem Cell Facility, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Lesch S; Department of Hematology, Oncology, and Tumor Immunology, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany., Movasshagi K; Department of Hematology, Oncology, and Tumor Immunology, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; Stem Cell Facility, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Tietze-Stolley C; Department of Hematology, Oncology, and Tumor Immunology, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; Stem Cell Facility, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Loyal L; BIH Center for Exploratory Diagnostic Sciences (EDS), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany.; Si-M/'Der Simulierte Mensch' a science framework of Technische Universität Berlin and Charite - Universitätsmedizin Berlin, Berlin, Germany.; Immunomics - Regenerative Immunology and Aging, Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany., Henze L; BIH Center for Exploratory Diagnostic Sciences (EDS), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany.; Si-M/'Der Simulierte Mensch' a science framework of Technische Universität Berlin and Charite - Universitätsmedizin Berlin, Berlin, Germany.; Immunomics - Regenerative Immunology and Aging, Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany., Penack O; Department of Hematology, Oncology, and Tumor Immunology, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany., Stervbo U; BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany.; Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany., Babel N; BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany.; Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany., Haas S; Department of Hematology, Oncology, and Tumor Immunology, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; BIH Center for Exploratory Diagnostic Sciences (EDS), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany.; German Cancer Consortium (DKTK), Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Beule D; Core Unit Bioinformatics (CUBI), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany., Bullinger L; Department of Hematology, Oncology, and Tumor Immunology, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; German Cancer Consortium (DKTK), Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; ECRC Experimental and Clinical Research Center, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany., Wittenbecher F; Department of Hematology, Oncology, and Tumor Immunology, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany., Na IK; Department of Hematology, Oncology, and Tumor Immunology, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany.; Si-M/'Der Simulierte Mensch' a science framework of Technische Universität Berlin and Charite - Universitätsmedizin Berlin, Berlin, Germany.; German Cancer Consortium (DKTK), Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; ECRC Experimental and Clinical Research Center, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2023 Feb 10; Vol. 14, pp. 1114368. Date of Electronic Publication: 2023 Feb 10 (Print Publication: 2023).
DOI: 10.3389/fimmu.2023.1114368
Abstrakt: The critical balance between intended and adverse effects in allogeneic hematopoietic stem cell transplantation (alloHSCT) depends on the fate of individual donor T-cells. To this end, we tracked αβT-cell clonotypes during stem cell mobilization treatment with granulocyte-colony stimulating factor (G-CSF) in healthy donors and for six months during immune reconstitution after transfer to transplant recipients. More than 250 αβT-cell clonotypes were tracked from donor to recipient. These clonotypes consisted almost exclusively of CD8 + effector memory T cells (CD8TEM), which exhibited a different transcriptional signature with enhanced effector and cytotoxic functions compared to other CD8TEM. Importantly, these distinct and persisting clonotypes could already be delineated in the donor. We confirmed these phenotypes on the protein level and their potential for selection from the graft. Thus, we identified a transcriptional signature associated with persistence and expansion of donor T-cell clonotypes after alloHSCT that may be exploited for personalized graft manipulation strategies in future studies.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Obermayer, Keilholz, Conrad, Frentsch, Blau, Vuong, Lesch, Movasshagi, Tietze-Stolley, Loyal, Henze, Penack, Stervbo, Babel, Haas, Beule, Bullinger, Wittenbecher and Na.)
Databáze: MEDLINE