T cell repertoire sequencing to study the contribution of different donor T cell subsets to patient repertoire at the early stage after αβT/CD19‐depleted allogeneic hematopoietic stem cell transplantation
αβT/CD19‐lymphocyte depletion allows decreasing the incidence of graft‐versus‐host disease after allogeneic hematopoietic stem cell transplantation (HSCT). The additional infusion of donor CD45RA‐depleted T cells (mDLI) can potentially compensate for the delayed immune reconstitution. Previously we’ve shown that during the first several months after αβT‐ depleted HSCT patients have extremely low T cell repertoire diversity, and T cell clones can be transferred with primary graft and/or mDLI. Here we used T cell repertoire sequencing to study the impact of different donor T cell subpopulations to the recipient repertoire early after αβT/CD19‐depleted HSCT with and without mDLI (n=11,n=8). βTCR clonotypes from donor primary graft, mDLI and FACS‐sorted CD4+, CD8+, Tscm(CD3+CCR7+CD95+CD127+), Tem(CD3+CCR7‐RO+), Tcm(CD3+CCR7+RO+) cells were tracked in recipient blood at d60 and d120 after HSCT. A relatively small number of donor T cell clones expanded enough to be detected in patient blood at 2 or 4 months after HSCT. More donor clones with higher initial T cell proportion were detected in patients transplanted with mDLI. However, the infusion of mDLI not resulted in higher repertoire diversity. Both, CD4+ and CD8+ T cells contributed to the early patient repertoire. Surprisingly, clones from T cells with high proliferative potential (Tscm) didn’t have a higher detection rate in patients. While the detection rate was higher for clonotypes from donor CD69+ T cells. Our results demonstrate that infusion of donor memory T cells enriches recipient repertoire after allogeneic HSCT, but other factors beyond initial clone size influence its survival and expansion.
Список научных проектов, где отмечена публикация
- Изучение эффекта адаптивного трансфера Т-клеток памяти донора на ранний репертуар Т-лимфоцитов реципиента при аллогенной ТГСК у детей (6 Января 2019 года 31 Декабря 2021 года). . Грант, РФФИ.


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