Karnell F G, Lin D, Motley S, Duhen T, Lim N, Campbell D J, Turka L A, Maecker H T, Harris K M
Immune Tolerance Network, Bethesda, MD, USA.
Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Clin Exp Immunol. 2017 Sep;189(3):268-278. doi: 10.1111/cei.12985. Epub 2017 Jun 7.
Multiple sclerosis is an inflammatory T cell-mediated autoimmune disease. In a Phase II clinical trial, high-dose immunosuppressive therapy combined with autologous CD34 haematopoietic stem cell transplant resulted in 69·2% of subjects remaining disease-free without evidence of relapse, loss of neurological function or new magnetic resonance imaging (MRI) lesions to year 5 post-treatment. A combination of CyTOF mass cytometry and multi-parameter flow cytometry was used to explore the reconstitution kinetics of immune cell subsets in the periphery post-haematopoietic cell transplant (HSCT) and the impact of treatment on the phenotype of circulating T cells in this study population. Repopulation of immune cell subsets progressed similarly for all patients studied 2 years post-therapy, regardless of clinical outcome. At month 2, monocytes and natural killer (NK) cells were proportionally more abundant, while CD4 T cells and B cells were reduced, relative to baseline. In contrast to the changes observed at earlier time-points in the T cell compartment, B cells were proportionally more abundant and expansion in the proportion of naive B cells was observed 1 and 2 years post-therapy. Within the T cell compartment, the proportion of effector memory and late effector subsets of CD4 and CD8 T cells was increased, together with transient increases in proportions of CD45RA-regulatory T cells (T ) and T helper type 1 (Th1 cells) and a decrease in Th17·1 cells. While none of the treatment effects studied correlated with clinical outcome, patients who remained healthy throughout the 5-year study had significantly higher absolute numbers of memory CD4 and CD8 T cells in the periphery prior to stem cell transplantation.
多发性硬化症是一种由炎症性T细胞介导的自身免疫性疾病。在一项II期临床试验中，高剂量免疫抑制疗法联合自体CD34造血干细胞移植使69.2%的受试者在治疗后5年保持无病状态，没有复发、神经功能丧失或新的磁共振成像（MRI）病变的证据。在本研究人群中，采用细胞飞行时间质谱流式细胞术和多参数流式细胞术相结合的方法，探讨造血细胞移植（HSCT）后外周免疫细胞亚群的重建动力学以及治疗对循环T细胞表型的影响。无论临床结果如何，所有研究患者在治疗后2年免疫细胞亚群的重建进展相似。在第2个月时，与基线相比，单核细胞和自然杀伤（NK）细胞的比例相对更高，而CD4 T细胞和B细胞减少。与在T细胞区室早期时间点观察到的变化相反，B细胞比例相对更高，并且在治疗后1年和2年观察到幼稚B细胞比例增加。在T细胞区室中，CD4和CD8 T细胞的效应记忆亚群和晚期效应亚群的比例增加，同时CD45RA调节性T细胞（T）和1型辅助性T细胞（Th1细胞）的比例短暂增加，而Th17·1细胞减少。虽然所研究的治疗效果均与临床结果无关，但在整个5年研究中保持健康的患者在干细胞移植前外周血中记忆性CD4和CD8 T细胞的绝对数量显著更高。
