Donor regulatory T cells rapidly adapt to recipient tissues to control murine acute graft-versus-host disease.

Autor: Dittmar DJ; Department of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany.; BioNTech SE, 82061, Neuried, Germany., Pielmeier F; Department of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany., Strieder N; Leibniz Institute for Immunotherapy, 93053, Regensburg, Germany., Fischer A; Department of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany., Herbst M; Department of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany.; Institute of Experimental Immunology, Research Unit Tumorimmunology, University of Zurich, Zurich, Switzerland., Stanewsky H; Department of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany., Wenzl N; Leibniz Institute for Immunotherapy, 93053, Regensburg, Germany., Röseler E; Leibniz Institute for Immunotherapy, 93053, Regensburg, Germany., Eder R; Department of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany., Gebhard C; Leibniz Institute for Immunotherapy, 93053, Regensburg, Germany., Schwarzfischer-Pfeilschifter L; Department of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany., Albrecht C; Department of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany., Herr W; Department of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany., Edinger M; Department of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany. matthias.edinger@ukr.de.; Leibniz Institute for Immunotherapy, 93053, Regensburg, Germany. matthias.edinger@ukr.de., Hoffmann P; Department of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany. petra.hoffmann@ukr.de.; Leibniz Institute for Immunotherapy, 93053, Regensburg, Germany. petra.hoffmann@ukr.de., Rehli M; Department of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany. michael.rehli@ukr.de.; Leibniz Institute for Immunotherapy, 93053, Regensburg, Germany. michael.rehli@ukr.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Apr 15; Vol. 15 (1), pp. 3224. Date of Electronic Publication: 2024 Apr 15.
DOI: 10.1038/s41467-024-47575-z
Abstrakt: The adoptive transfer of regulatory T cells is a promising strategy to prevent graft-versus-host disease after allogeneic bone marrow transplantation. Here, we use a major histocompatibility complex-mismatched mouse model to follow the fate of in vitro expanded donor regulatory T cells upon migration to target organs. Employing comprehensive gene expression and repertoire profiling, we show that they retain their suppressive function and plasticity after transfer. Upon entering non-lymphoid tissues, donor regulatory T cells acquire organ-specific gene expression profiles resembling tissue-resident cells and activate hallmark suppressive and cytotoxic pathways, most evidently in the colon, when co-transplanted with graft-versus-host disease-inducing conventional T cells. Dominant T cell receptor clonotypes overlap between organs and across recipients and their relative abundance correlates with protection efficacy. Thus, this study reveals donor regulatory T cell selection and adaptation mechanisms in target organs and highlights protective features of Treg to guide the development of improved graft-versus-host disease prevention strategies.
(© 2024. The Author(s).)
Databáze: MEDLINE
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