Identification of the immunological profile in rejection-free heart transplantation

Tolerance induction following organ transplantation can be achieved by adoptive cell transfer of regulatory T-cells (Tregs) 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). 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, Tregs, 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. 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 Tregs and of their CD62L+ subset was reduced in LT-HTx patients (%Tregs: 9.1 ± 3.7%, p = .026; %CD62L+: 85.1 ± 11.9%, p = .009) compared to pre-HTx patients (%Tregs: 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+ Tregs had the strongest influence to distinguish among long-term rejection-free and pre-HTx patients. 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.