Background

Tolerance induction following organ transplantation can be achieved by adoptive cell transfer of regulatory T-cells (T_regs) or dendritic cells (DCs). However, the target immunological profile is unknown. The present study aimed to identify an immunological profile connected to tolerance induction following heart transplantation (HTx).

Methods

Blood samples of long-term rejection-free HTx patients (LT-HTx, n = 20) and patients on the HTx waiting list (pre-HTx, n = 20) were compared. Flow cytometric and multiplex analyses of DCs, T_regs, subsets of both cell types and serum cytokines were performed. Furthermore, principle component and cluster analysis was used to identify a target immunological profile using a multiparametric dataset.

Results

Plasmacytoid DCs expressing blood DC antigen (BDCA) 2 and BDCA4 were significantly increased in LT-HTx patients (BDCA2⁺: 29.4 ± 10.1%, p = .022; BDCA4⁺: 26.4 ± 9.3%, p = .008) compared to pre-HTx patients (BDCA2⁺: 22.8 ± 7.2%; BDCA4⁺: 18.9 ± 7.4%). The percentage of total T_regs and of their CD62L⁺ subset was reduced in LT-HTx patients (%T_regs: 9.1 ± 3.7%, p = .026; %CD62L⁺: 85.1 ± 11.9%, p = .009) compared to pre-HTx patients (%T_regs: 11.8 ± 3.6%; %CD62L⁺: 93.3 ± 4.5%). LT-HTx patients showed different cytokine levels than pre-HTx patients. Principle component and cluster analysis revealed that the total DCs, BDCA2⁺ and BDCA4⁺ DCs and CD147⁺ T_regs had the strongest influence to distinguish among long-term rejection-free and pre-HTx patients.

Conclusion

In conclusion, we defined the immune status of pre-HTx patients and the target immunological profile of LT-HTx patients. These data may help to establish a monitoring tool that is based on a multiparametric dataset.

中文翻译：

---

无排斥性心脏移植中免疫学特征的鉴定。

背景

器官移植后的耐受诱导可以通过调节性T细胞（T _regs）或树突状细胞（DCs）的过继细胞转移来实现。但是，靶免疫学特征是未知的。本研究旨在确定与心脏移植（HTx）后的耐受性诱导相关的免疫学特征。

方法

比较了长期无排斥的HTx患者（LT-HTx，n  = 20）和HTx等待名单中的患者（HTx之前，n = 20）的血液样本。进行了DC，T _regs，两种细胞类型的子集和血清细胞因子的流式细胞术和多重分析。此外，主成分和聚类分析用于使用多参数数据集识别目标免疫学特征。

结果

与LT-HTx患者相比，表达血液DC抗原（BDCA）2和BDCA4的浆细胞样DC显着增加（BDCA2 ⁺：29.4±10.1％，p  = .022; BDCA4 ⁺：26.4±9.3％，p  = .008） -HTx患者（BDCA2 ⁺：22.8±7.2％; BDCA4 ⁺：18.9±7.4％）。与LT-HTx患者相比，总T _regs及其CD62L ⁺子集的百分比降低了（％T _regs：9.1±3.7％，p  = .026；％CD62L ⁺：85.1±11.9％，p  = .009） HTx前患者（％T _regs：11.8±3.6％;％CD62L ⁺：93.3±4.5％）。LT-HTx患者显示的细胞因子水平与HTx之前患者不同。主成分和聚类分析表明，总的DC，BDCA2 ⁺和BDCA4 ⁺ DC和CD147 ⁺ Ť_暂存器具有最强影响长期排斥和无预个HTx患者之间进行区分。

结论

总之，我们定义了HT-HTx前患者的免疫状况和LT-HTx患者的目标免疫学特征。这些数据可能有助于建立基于多参数数据集的监视工具。