Department of Brain Sciences, Imperial College London, London, United Kingdom; Department of Neurosciences, Drug and Child Health, University of Florence, Florence, Italy.
Department of Brain Sciences, Imperial College London, London, United Kingdom.
Handb Clin Neurol. 2024;202:55-74. doi: 10.1016/B978-0-323-90242-7.00003-1.
Hematopoietic stem cell transplantation (HSCT) is a multistep procedure aimed at eradicating the immune system and replacing it with a new one reconstituted from hematopoietic stem cells which in autologous HSCT (AHSCT) have previously been harvested from the same individual. Over the last two decades, AHSCT has been developed as a treatment option for people affected by aggressive multiple sclerosis (MS), and it exerts a long-standing effect on new inflammation-driven disease activity. The rationale for the use of AHSCT in MS will be discussed, starting from the first observations on experimental models. The mechanisms and kinetics of repopulation (i.e., quantitative recovery) and reconstitution (i.e., qualitative changes) of the immune cell populations will be explored, focusing on immune reconstitution of the T and B cells compartments and briefly covering changes in the innate immune system. Finally, potential immunologic markers of response to treatment will be reviewed. Insights into the supposed mechanism(s) of action of AHSCT will be provided, discussing the leading hypothesis of the "rebuilding" of a newly tolerant immune system, and examining the apparent paradox of the long-standing control of disease activity despite a relatively short-term immunosuppressive effect of the procedure.
造血干细胞移植（HSCT）是一个多步骤的过程，旨在消除免疫系统，并将其替换为新的免疫系统，这些新的免疫系统由造血干细胞组成，而在自体 HSCT（AHSCT）中，这些造血干细胞先前已从同一患者中采集。在过去的二十年中，AHSCT 已被开发为一种治疗侵袭性多发性硬化症（MS）的方法，它对新的炎症驱动的疾病活动具有长期的影响。将从实验模型的最初观察结果开始，讨论在 MS 中使用 AHSCT 的基本原理。将探讨免疫细胞群的再定居（即定量恢复）和重建（即定性变化）的机制和动力学，重点关注 T 和 B 细胞区室的免疫重建，并简要涵盖固有免疫系统的变化。最后，将回顾潜在的免疫治疗反应标志物。将提供对 AHSCT 作用机制的假设的深入了解，讨论“重建”新的耐受免疫系统的主要假设，并研究尽管该过程具有相对短期的免疫抑制作用，但长期控制疾病活动的明显悖论。
