Human skin-resident host T cells can persist long term after allogeneic stem cell transplantation and maintain recirculation potential.

Autor:	de Almeida GP; Institute of Virology, Technical University of Munich, Munich, Germany.; TranslaTUM, Technical University of Munich, Munich, Germany.; German Center for Infection Research partner site, Munich, Germany., Lichtner P; Genome Analysis Center, Helmholtz Zentrum Munich, Munich, Germany., Eckstein G; Genome Analysis Center, Helmholtz Zentrum Munich, Munich, Germany., Brinkschmidt T; Institute of Virology, Technical University of Munich, Munich, Germany.; TranslaTUM, Technical University of Munich, Munich, Germany.; Department of Infection Immunology, Leibniz-Institute for Natural Product Research and Infection Biology, Jena, Germany., Chu CF; TranslaTUM, Technical University of Munich, Munich, Germany.; Department of Infection Immunology, Leibniz-Institute for Natural Product Research and Infection Biology, Jena, Germany.; Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University, Jena, Germany., Sun S; Institute of Virology, Technical University of Munich, Munich, Germany.; TranslaTUM, Technical University of Munich, Munich, Germany.; German Center for Infection Research partner site, Munich, Germany.; Department of Infection Immunology, Leibniz-Institute for Natural Product Research and Infection Biology, Jena, Germany., Reinhard J; TranslaTUM, Technical University of Munich, Munich, Germany., Mädler SC; TranslaTUM, Technical University of Munich, Munich, Germany., Kloeppel M; Klinikum rechts der Isar and Praxisklinik für Ästhetische Chirurgie und Medizin, Munich, Germany., Verbeek M; Department of Medicine III, Klinikum rechts der Isar, Munich, Germany., Zielinski CE; Institute of Virology, Technical University of Munich, Munich, Germany.; TranslaTUM, Technical University of Munich, Munich, Germany.; German Center for Infection Research partner site, Munich, Germany.; Department of Infection Immunology, Leibniz-Institute for Natural Product Research and Infection Biology, Jena, Germany.; Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University, Jena, Germany.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2022 Jan 28; Vol. 7 (67), pp. eabe2634. Date of Electronic Publication: 2022 Jan 28.
DOI:	10.1126/sciimmunol.abe2634
Abstrakt:	Tissue-resident memory T cells (T RM ) have recently emerged as crucial cellular players for host defense in a wide variety of tissues and barrier sites. Insights into the maintenance and regulatory checkpoints of human T RM cells remain scarce, especially due to the difficulties associated with tracking T cells through time and space in humans. We therefore sought to identify and characterize skin-resident T cells in humans defined by their long-term in situ lodgment. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) preceded by myeloablative chemotherapy unmasked long-term sequestration of host T cell subsets in human skin despite complete donor T cell chimerism in the blood. Single-cell chimerism analysis paired with single-cell transcriptional profiling comprehensively characterized these bona fide long-term skin-resident T cells and revealed differential tissue maintenance for distinct T cell subsets, specific T RM cell markers such as galectin-3, but also tissue exit potential with retention of the transcriptomic T RM cell identity. Analysis of 26 allo-HSCT patients revealed profound interindividual variation in the tissue maintenance of host skin T cells. The long-term persistence of host skin T cells in a subset of these patients did not correlate with the development of chronic GvHD. Our data exemplify the power of exploiting a clinical situation as a proof of concept for the existence of bona fide human skin T RM cells and reveal long-term persistence of host T cells in a peripheral tissue but not in the circulation or bone marrow in a subset of allo-HSCT patients.
Databáze:	MEDLINE
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