Graft-versus-host disease prophylaxis shapes T cell biology and immune reconstitution after hematopoietic cell transplant.

PT-Cy-based GVHD prophylaxis causes a T cell diversity bottleneck, reducing TCR repertoire diversity for 2 years posttransplant compared to Tac/MTX.

• Why it matters: Understanding how different immunosuppressive regimens influence T cell reconstitution is crucial for improving transplant outcomes and managing complications like GVHD and infections.
• What they did: The study analyzed 2359 longitudinal T cell samples from 324 patients, using TCR sequencing to compare T cell reconstitution pathways between PT-Cy and Tac/MTX regimens, focusing on TCR diversity and pathogen-specific TCR depletion.
• The result: PT-Cy was linked to delayed T cell expansion and reduced TCR diversity, which was associated with protection against chronic GVHD but also increased risk of severe infection due to depletion of pathogen-specific TCRs.