Eur J Immunol, 2021, 51(S1):1-448

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.

Zvyagin IV, Blagov S, Fomchenkova V, Fadeeva M, Komech EA, Zhogov V, Barinova AA, Mikelov AI, Sycheva AL, Lebedev YB, Maschan MA

IBCH: 9847
Ссылка на статью в журнале: https://onlinelibrary.wiley.com/doi/10.1002/eji.202170200
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