Vadakekolathu Jayakumar, Rutella Sergio
John van Geest Cancer Research Centre, Nottingham Trent University, Clifton Lane NG11 8NS, UK.
Biomedicines. 2017 Jun 21;5(2):33. doi: 10.3390/biomedicines5020033.
Allogeneic haematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical donor can be curative for eligible patients with non-malignant and malignant haematological disorders. HSCT from alternative donor sources, such as HLA-mismatched haploidentical donors, is increasingly considered as a viable therapeutic option for patients lacking HLA-matched donors. Initial attempts at haploidentical HSCT were associated with vigorous bidirectional alloreactivity, leading to unacceptably high rates of graft rejection and graft-versus-host disease (GVHD). More recently, new approaches for mitigating harmful T-cell alloreactivity that mediates GVHD, while preserving the function of tumour-reactive natural killer (NK) cells and γδ T cells, have led to markedly improved clinical outcomes, and are successfully being implemented in the clinic. This article will provide an update on in vitro strategies and in vivo approaches aimed at preventing GVHD by selectively manipulating key components of the adaptive immune response, such as T-cell receptor (TCR)-αβ T cells and CD45RA-expressing naive T cells.
来自人类白细胞抗原（HLA）匹配供体的异基因造血干细胞移植（HSCT）对于符合条件的非恶性和恶性血液系统疾病患者可能具有治愈作用。来自其他供体来源的HSCT，如HLA不匹配的单倍体相合供体，越来越被视为缺乏HLA匹配供体患者的一种可行治疗选择。早期单倍体相合HSCT尝试与强烈的双向同种异体反应性相关，导致移植排斥和移植物抗宿主病（GVHD）发生率高得令人无法接受。最近，减轻介导GVHD的有害T细胞同种异体反应性同时保留肿瘤反应性自然杀伤（NK）细胞和γδT细胞功能的新方法，已使临床结果显著改善，并正在临床上成功应用。本文将提供有关体外策略和体内方法的最新进展，这些策略和方法旨在通过选择性操纵适应性免疫反应的关键成分，如T细胞受体（TCR）αβT细胞和表达CD45RA的初始T细胞，来预防GVHD。
