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Post-transplant cyclophosphamide prevents xenogeneic graft-versus-host disease while depleting proliferating regulatory T cells
Graft-versus-host disease (GVHD) remains a serious limitation of allogeneic hematopoietic cell transplantation (allo-HCT). While post-transplant administration of cyclophosphamide (PTCy) is increasingly used as GVHD prophylaxis, its precise mechanisms of action and its impact on graft-versus-leukemi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9947306/ https://www.ncbi.nlm.nih.gov/pubmed/36843851 http://dx.doi.org/10.1016/j.isci.2023.106085 |
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author | Ritacco, Caroline Köse, Murat Cem Courtois, Justine Canti, Lorenzo Beguin, Charline Dubois, Sophie Vandenhove, Benoît Servais, Sophie Caers, Jo Beguin, Yves Ehx, Grégory Baron, Frédéric |
author_facet | Ritacco, Caroline Köse, Murat Cem Courtois, Justine Canti, Lorenzo Beguin, Charline Dubois, Sophie Vandenhove, Benoît Servais, Sophie Caers, Jo Beguin, Yves Ehx, Grégory Baron, Frédéric |
author_sort | Ritacco, Caroline |
collection | PubMed |
description | Graft-versus-host disease (GVHD) remains a serious limitation of allogeneic hematopoietic cell transplantation (allo-HCT). While post-transplant administration of cyclophosphamide (PTCy) is increasingly used as GVHD prophylaxis, its precise mechanisms of action and its impact on graft-versus-leukemia effects have remained debated. Here, we studied the mechanisms of xenogeneic GVHD (xGVHD) prevention by PTCy in different humanized mouse models. We observed that PTCy attenuated xGVHD. Using flow cytometry and single-cell RNA-sequencing, we demonstrated that PTCy depleted proliferative CD8(+) and conventional CD4(+) T cells but also proliferative regulatory T cells (Treg). Further, T-cell receptor β variable region sequencing (TCRVB) analyses demonstrated that highly xenoreactive T-cell clones were depleted by PTCy. Although Treg frequencies were significantly higher in PTCy-treated than in control mice on day 21, xGVHD attenuation by PTCy was not abrogated by Treg depletion. Finally, we observed that PTCy did not abrogate graft-versus-leukemia effects. |
format | Online Article Text |
id | pubmed-9947306 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-99473062023-02-24 Post-transplant cyclophosphamide prevents xenogeneic graft-versus-host disease while depleting proliferating regulatory T cells Ritacco, Caroline Köse, Murat Cem Courtois, Justine Canti, Lorenzo Beguin, Charline Dubois, Sophie Vandenhove, Benoît Servais, Sophie Caers, Jo Beguin, Yves Ehx, Grégory Baron, Frédéric iScience Article Graft-versus-host disease (GVHD) remains a serious limitation of allogeneic hematopoietic cell transplantation (allo-HCT). While post-transplant administration of cyclophosphamide (PTCy) is increasingly used as GVHD prophylaxis, its precise mechanisms of action and its impact on graft-versus-leukemia effects have remained debated. Here, we studied the mechanisms of xenogeneic GVHD (xGVHD) prevention by PTCy in different humanized mouse models. We observed that PTCy attenuated xGVHD. Using flow cytometry and single-cell RNA-sequencing, we demonstrated that PTCy depleted proliferative CD8(+) and conventional CD4(+) T cells but also proliferative regulatory T cells (Treg). Further, T-cell receptor β variable region sequencing (TCRVB) analyses demonstrated that highly xenoreactive T-cell clones were depleted by PTCy. Although Treg frequencies were significantly higher in PTCy-treated than in control mice on day 21, xGVHD attenuation by PTCy was not abrogated by Treg depletion. Finally, we observed that PTCy did not abrogate graft-versus-leukemia effects. Elsevier 2023-01-31 /pmc/articles/PMC9947306/ /pubmed/36843851 http://dx.doi.org/10.1016/j.isci.2023.106085 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Ritacco, Caroline Köse, Murat Cem Courtois, Justine Canti, Lorenzo Beguin, Charline Dubois, Sophie Vandenhove, Benoît Servais, Sophie Caers, Jo Beguin, Yves Ehx, Grégory Baron, Frédéric Post-transplant cyclophosphamide prevents xenogeneic graft-versus-host disease while depleting proliferating regulatory T cells |
title | Post-transplant cyclophosphamide prevents xenogeneic graft-versus-host disease while depleting proliferating regulatory T cells |
title_full | Post-transplant cyclophosphamide prevents xenogeneic graft-versus-host disease while depleting proliferating regulatory T cells |
title_fullStr | Post-transplant cyclophosphamide prevents xenogeneic graft-versus-host disease while depleting proliferating regulatory T cells |
title_full_unstemmed | Post-transplant cyclophosphamide prevents xenogeneic graft-versus-host disease while depleting proliferating regulatory T cells |
title_short | Post-transplant cyclophosphamide prevents xenogeneic graft-versus-host disease while depleting proliferating regulatory T cells |
title_sort | post-transplant cyclophosphamide prevents xenogeneic graft-versus-host disease while depleting proliferating regulatory t cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9947306/ https://www.ncbi.nlm.nih.gov/pubmed/36843851 http://dx.doi.org/10.1016/j.isci.2023.106085 |
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