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 alpha beta T-cell clonotypes during stem cell mobilization treatment with granulocyte-colony stimulating factor (G-CSF) in healthy donors and for six months during immune reconstitution after transfer to transplant recipients. More than 250 alpha beta T-cell clonotypes were tracked from donor to recipient. These clonotypes 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 clonotypes 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 clonotypes after alloHSCT that may be exploited for personalized graft manipulation strategies in future studies.

Automated summary

The fate of individual donor T-cells is crucial for the balance between intended and adverse effects in allogeneic hematopoietic stem cell transplantation (alloHSCT). In this study, we tracked alpha beta T-cell clonotypes during stem cell mobilization and immune reconstitution after transplant. We found over 250 alpha beta T-cell clonotypes that consisted mainly of CD8(+) effector memory T cells. These clonotypes showed a distinct transcriptional signature and enhanced effector and cytotoxic functions.