Cytotherapy · 2025
Impact of ATLG on CD4+ T-cell reconstitution after HSCT in children: a detailed immune profiling study.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Sindoni Marco M, Toso Anita, Limido Francesca, Bugarin Cristina, Villa Tiziana, Bonte Sarah, Saeys Yvan, Buracchi Chiara, Prunotto Giulia, Meda Spaccamela Virginia, Hauri Mathias, Maglia Oscar, Sala Simona, Gaspari Domenico, Fazio Grazia, Biondi Andrea, Balduzzi Adriana, Nucera Silvia, Gaipa Giuseppe
Аннотация
INTRODUCTION: Graft versus host disease (GvHD) prophylaxis impacts on post-hematopoietic stem cell transplantation (HSCT) immune reconstitution (IR). Specifically, anti-T lymphocyte globulin (ATLG) delays CD4+ T cell reconstitution. However, the mechanism by which ATLG alters the composition of CD4+ T-cell compartments remains elusive.
AIMS: Dissect the impact of ATLG on CD4+ T cells by integrating advanced and highly standardized flow cytometric panels, unsupervised clustering analysis, machine learning approaches, and molecular biology techniques.
RESULTS: We analyzed post-HSCT IR in 94 pediatric patients with a machine learning approach. ATLG exposure resulted in the most relevant variable affecting CD4+ T-cell counts. Severe combined immunodeficiency/recent thymic emigrant (SCID/RTE) and CD4 PERISCOPE EuroFlow antibody panels were applied to a sub-cohort of patients with acute lymphoblastic leukemia. Unsupervised clustering analysis showed that in the first months, post-HSCT CD4+ naïve T cells and RTEs were significantly reduced in ATLG-treated compared to no-ATLG patients, including haploidentical graft recipients receiving post-transplant cyclophosphamide. In no-ATLG patients, there was a significant contribution of residual recipient-derived cells to the RTE compartment, whereas in ATLG-treated patients RTEs were of donor origin. In addition, in no-ATLG patients, early RTEs and CD4+ T-cell counts correlated with infused CD3+ T cells/kg. Bone marrow and T-cell receptor excision circle (TREC) analysis showed that ATLG treatment does not affect early T-cell maturation. In vitro testing showed increased differentiation of naïve/RTE CD4+ into effector subsets upon ATLG exposure, confirmed by flow cytometry and RNA sequencing.
DISCUSSION: Our data show that ATLG induces concomitant differentiation and depletion of the peripheral CD4+ naïve/RTE T-cell compartment. Together, these findings suggest that naïve T-cell reconstitution after ATLG is delayed since it only relies on thymic maturation, differently from no-ATLG treated patients.
AIMS: Dissect the impact of ATLG on CD4+ T cells by integrating advanced and highly standardized flow cytometric panels, unsupervised clustering analysis, machine learning approaches, and molecular biology techniques.
RESULTS: We analyzed post-HSCT IR in 94 pediatric patients with a machine learning approach. ATLG exposure resulted in the most relevant variable affecting CD4+ T-cell counts. Severe combined immunodeficiency/recent thymic emigrant (SCID/RTE) and CD4 PERISCOPE EuroFlow antibody panels were applied to a sub-cohort of patients with acute lymphoblastic leukemia. Unsupervised clustering analysis showed that in the first months, post-HSCT CD4+ naïve T cells and RTEs were significantly reduced in ATLG-treated compared to no-ATLG patients, including haploidentical graft recipients receiving post-transplant cyclophosphamide. In no-ATLG patients, there was a significant contribution of residual recipient-derived cells to the RTE compartment, whereas in ATLG-treated patients RTEs were of donor origin. In addition, in no-ATLG patients, early RTEs and CD4+ T-cell counts correlated with infused CD3+ T cells/kg. Bone marrow and T-cell receptor excision circle (TREC) analysis showed that ATLG treatment does not affect early T-cell maturation. In vitro testing showed increased differentiation of naïve/RTE CD4+ into effector subsets upon ATLG exposure, confirmed by flow cytometry and RNA sequencing.
DISCUSSION: Our data show that ATLG induces concomitant differentiation and depletion of the peripheral CD4+ naïve/RTE T-cell compartment. Together, these findings suggest that naïve T-cell reconstitution after ATLG is delayed since it only relies on thymic maturation, differently from no-ATLG treated patients.