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

David J. Dittmar, Franziska Pielmeier, Nicholas Strieder, Alexander Fischer, Michael Herbst, Hanna Stanewsky, Niklas Wenzl, Eveline Röseler, Rüdiger Eder, Claudia Gebhard, Lucia Schwarzfischer-Pfeilschifter, Christin Albrecht, Wolfgang Herr, Matthias Edinger (), Petra Hoffmann () and Michael Rehli ()
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David J. Dittmar: University Hospital Regensburg
Franziska Pielmeier: University Hospital Regensburg
Nicholas Strieder: Leibniz Institute for Immunotherapy
Alexander Fischer: University Hospital Regensburg
Michael Herbst: University Hospital Regensburg
Hanna Stanewsky: University Hospital Regensburg
Niklas Wenzl: Leibniz Institute for Immunotherapy
Eveline Röseler: Leibniz Institute for Immunotherapy
Rüdiger Eder: University Hospital Regensburg
Claudia Gebhard: Leibniz Institute for Immunotherapy
Lucia Schwarzfischer-Pfeilschifter: University Hospital Regensburg
Christin Albrecht: University Hospital Regensburg
Wolfgang Herr: University Hospital Regensburg
Matthias Edinger: University Hospital Regensburg
Petra Hoffmann: University Hospital Regensburg
Michael Rehli: University Hospital Regensburg

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-47575-z

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