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Transcriptional profiling and single-cell chimerism analysis identifies human tissue resident T cells in the human skin after allogeneic stem cell transplantation

Gustavo P. de Almeida, Peter Lichtner, Sophia Mädler, Chang-Feng Chu, Christina E. Zielinski
doi: https://doi.org/10.1101/2020.04.11.037101
Gustavo P. de Almeida
1Institute of Virology, Technical University of Munich, Germany
2TranslaTUM, Technical University of Munich, Germany
3German Center for Infection Research, Munich, Germany
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Peter Lichtner
4Genome Analysis Center, Helmholtz Zentrum Munich, Germany
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Sophia Mädler
1Institute of Virology, Technical University of Munich, Germany
2TranslaTUM, Technical University of Munich, Germany
3German Center for Infection Research, Munich, Germany
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Chang-Feng Chu
1Institute of Virology, Technical University of Munich, Germany
2TranslaTUM, Technical University of Munich, Germany
3German Center for Infection Research, Munich, Germany
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Christina E. Zielinski
1Institute of Virology, Technical University of Munich, Germany
2TranslaTUM, Technical University of Munich, Germany
3German Center for Infection Research, Munich, Germany
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  • For correspondence: christina.zielinski@tum.de
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Abstract

Tissue resident memory T cells (TRM) have recently emerged as crucial cellular players for host defense in a wide variety of tissues and barrier sites. Mouse models revealed that they are maintained long-term in loco unlike recirculating effector memory T cells (TEM). Insights into the maintenance and regulatory checkpoints of human tissue resident T cells (TRM) remain scarce, especially due to the obstacles in tracking T cells over time and system-wide in humans. We present a clinical model that allowed us to overcome these limitations. We demonstrate that allogeneic stem cell transplantation resulted in compartmentalization of host T cells in the human skin despite complete donor T cell chimerism in the blood, thus unmasking long-term persistence of tissue resident T cell subsets of host origin within the diverse skin T cell community. Single-cell transcriptional profiling paired with single-cell chimerism analysis provided an in-depth characterization of these bona fide skin resident T cells. Their phenotype, functions and regulatory checkpoints may serve therapeutic strategies for the treatment of autoimmune diseases and chronic infections, where their specific depletion versus maintenance, respectively, will have to be harnessed pharmaceutically.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 13, 2020.
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Transcriptional profiling and single-cell chimerism analysis identifies human tissue resident T cells in the human skin after allogeneic stem cell transplantation
Gustavo P. de Almeida, Peter Lichtner, Sophia Mädler, Chang-Feng Chu, Christina E. Zielinski
bioRxiv 2020.04.11.037101; doi: https://doi.org/10.1101/2020.04.11.037101
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Transcriptional profiling and single-cell chimerism analysis identifies human tissue resident T cells in the human skin after allogeneic stem cell transplantation
Gustavo P. de Almeida, Peter Lichtner, Sophia Mädler, Chang-Feng Chu, Christina E. Zielinski
bioRxiv 2020.04.11.037101; doi: https://doi.org/10.1101/2020.04.11.037101

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