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Dittmar, David J; Pielmeier, Franziska; Strieder, Nicholas; Fischer, Alexander; Herbst, Michael; Stanewsky, Hanna; Wenzl, Niklas; Röseler, Eveline; Eder, Rüdiger; Gebhard, Claudia; Schwarzfischer-Pfeilschifter, Lucia; Albrecht, Christin; Herr, Wolfgang; Edinger, Matthias; Hoffmann, Petra; Rehli, Michael
Nature communications, 04/2024, Letnik: 15, Številka: 1Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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