Single-cell clonal tracking of persistent T-cells in allogeneic hematopoietic stem cell transplantation

The critical balance between intended and adverse effects in allogeneic hematopoietic stem cell transplantation (alloHSCT) depends on the fate of individual donor T‐cells. To this end, we tracked αβT‐cell clones during stem cell mobilization treatment with granulocyte-colony stimulating factor (G-CSF) in healthy donors and during immune reconstitution after transfer to transplant recipients. More than 250 αβT‐cell clones were tracked from donor to recipient. These clones consisted almost exclusively of CD8+ effector memory T cells (CD8TEM), which exhibited a different transcriptional signature with enhanced effector and cytotoxic functions compared to other CD8TEM. Importantly, these distinct and persisting clones could already be delineated in the donor. We confirmed these phenotypes on the protein level and their potential for selection from the graft. Thus, we identified a transcriptional signature associated with persistence and expansion of donor T-cell clones after alloHSCT that may be exploited for personalized graft manipulation strategies in future studies. We designed our study to analyze peripheral blood lymphocytes of paired donor and recipient samples. We included five alloHSCT patients between December 2018 and May 2019 who received PB grafts from related donors at the Charité Universitätsmedizin Berlin. Patients were only included if the respective donors could be included as well. Blood samples were collected from donors before G-CSF mobilization and on the day of apheresis. Recipient samples were collected on days +90 and +180 post transplantation. **RAW data not provided due to patient privacy concerns**