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

Benedikt Obermayer; Luisa Keilholz; Thomas Conrad; Marco Frentsch; Igor-Wolfgang Blau; Lam Vuong; Stella Lesch; Kamran Movasshagi; Carola Tietze-Stolley; Lucie Loyal; Larissa Henze; Olaf Penack; Ulrik Stervbo; Nina Babel; Simon Haas; Dieter Beule; Lars Bullinger; Friedrich Wittenbecher; Il-Kang Na

doi:10.3389/fimmu.2023.1114368

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

Front Immunol. 2023 Feb 10:14:1114368. doi: 10.3389/fimmu.2023.1114368. eCollection 2023.

Authors

Benedikt Obermayer¹, Luisa Keilholz^{2

3}, Thomas Conrad^{4

5}, Marco Frentsch^{2

3}, Igor-Wolfgang Blau², Lam Vuong^{2

6}, Stella Lesch^{2

3}, Kamran Movasshagi^{2

6}, Carola Tietze-Stolley^{2

6}, Lucie Loyal^{7

8

9}, Larissa Henze^{7

8

9}, Olaf Penack^{2

3}, Ulrik Stervbo^{3

10}, Nina Babel^{3

10}, Simon Haas^{2

7

11}, Dieter Beule¹, Lars Bullinger^{2

11

12}, Friedrich Wittenbecher^{2

3}, Il-Kang Na^{2

3

8

11

12}

Affiliations

¹ Core Unit Bioinformatics (CUBI), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany.
² Department of Hematology, Oncology, and Tumor Immunology, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany.
⁴ Core Unit Genomics, Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany.
⁵ Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
⁶ Stem Cell Facility, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁷ BIH Center for Exploratory Diagnostic Sciences (EDS), Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany.
⁸ Si-M/"Der Simulierte Mensch" a science framework of Technische Universität Berlin and Charite - Universitätsmedizin Berlin, Berlin, Germany.
⁹ Immunomics - Regenerative Immunology and Aging, Berlin Institute of Health at Charite - Universitätsmedizin Berlin, Berlin, Germany.
¹⁰ Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany.
¹¹ German Cancer Consortium (DKTK), Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹² ECRC Experimental and Clinical Research Center, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.

Abstract

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.

Keywords: T-cells; allogeneic HSCT; clonal tracking; leukemia; scRNAseq; transplantation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Tracking
Drug-Related Side Effects and Adverse Reactions*
Hematopoietic Stem Cell Mobilization
Hematopoietic Stem Cell Transplantation*
Humans
Stem Cell Transplantation

Grants and funding

The work was supported by grants from BIH and research funding from the Stiftung Charité (BIH Johanna Quandt funding).