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ALT Successful hematopoietic cell transplantation (HCT) requires immunosuppression to prevent graft-versus-host disease (GVHD), but the choice of regimen may shape immune reconstitution and GVHD risk. DeWolf et al. analyzed the T cell repertoires of clinical trial participants who received either tacrolimus and methotrexate (Tac/MTX) or posttransplant cyclophosphamide, mycophenolate mofetil, and tacrolimus (PT-Cy) as GVHD prophylaxis after HCT. PT-Cy more profoundly depleted the T cell compartment, creating a bottleneck as depicted on the cover, which resulted in a less diverse T cell repertoire. This reduced diversity was associated with lower GVHD risk but higher risk of infection after transplant. These findings show that immunosuppressive regimens can shape the balance between beneficial and harmful outcomes of HCT. Credit: N. Burgess/Science Translational Medicine




















