Mass cytometry reveals a distinct immunoprofile of operational tolerance in pediatric liver transplantation.
Mass cytometry reveals a distinct immunoprofile of operational tolerance in pediatric liver transplantation.
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DOI：
10.1111/petr.12795
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发表时间：
2016-12
影响因子：
1.3
通讯作者：
Krams SM
中科院分区：
文献类型：
--
作者：
Lau AH;Vitalone MJ;Haas K;Shawler T;Esquivel CO;Berquist WE;Martinez OM;Castillo RO;Krams SM
移植患者长期免疫抑制具有显著的发病率、较差的生活质量和巨大的经济成本。手术耐受，定义为在没有免疫抑制的情况下移植物接受而没有功能损害，已经在一些儿科肝移植受者中实现。使用质谱流式细胞术，外周血免疫分型进行表征耐受患者和单药免疫抑制稳定的患者之间的差异。使用来自手术耐受患者的单中心儿科肝移植人群的血液样本进行单细胞质量细胞计数，以全面表征与慢性低剂量免疫抑制患者相比耐受状态下的免疫细胞群。通过流式细胞术确认感兴趣的特异性T细胞群。这种高维表型分析揭示了移植人群之间不同的免疫特征，以及与儿科肝移植受者耐受性相关的操作耐受性（TOT; CD 4 + CD 5 + CD 25 + CD 38 −/loCD 45 RA）的CD 4 + T细胞亚群。与低水平免疫抑制稳定的患者相比，手术耐受患者的TOT显著增加。这种TOT细胞通过流式细胞术证实，并且不同于经典的T调节细胞。这些结果证明了质谱细胞术发现具有诊断潜力的显著免疫细胞特征的能力。
Long-term immunosuppression in transplant patients has significant morbidity, poorer quality of life, and substantial economic costs. Operational tolerance, defined as graft acceptance without functional impairment in the absence of immunosuppression, has been achieved in some pediatric liver transplant recipients. Using mass cytometry, peripheral blood immunotyping was performed to characterize differences between tolerant patients and patients who are stable on single-agent immunosuppression. Single-cell mass cytometry was performed using blood samples from a single-center pediatric liver transplant population of operationally tolerant patients to comprehensively characterize the immune cell populations in the tolerant state compared to patients on chronic low dose immunosuppression. Specific T cell populations of interest were confirmed by flow cytometry. This high dimensional phenotypic analysis revealed distinct immunoprofiles between transplant populations as well as a CD4+ T cell subset of Operational Tolerance (TOT; CD4+CD5+CD25+CD38−/loCD45RA) that correlates with tolerance in pediatric liver transplant recipients. In operationally tolerant patients the TOT was significantly increased as compared to patients stable on low levels of immunosuppression. This TOT cell was confirmed by flow cytometry and is distinct from classic T regulatory cells. These results demonstrate the power of mass cytometry to discover significant immune cell signatures that have diagnostic potential.