Post-transplant cyclophosphamide prevents xenogeneic graft-versus-host disease while depleting proliferating regulatory T cells.

ABSTRACT: 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 xenorea

SUBMITTER: Ritacco C 

PROVIDER: S-EPMC9947306 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature