Specific Immune Tolerance Response Triggered by Extracorporal Photopheresis after Heart Transplantation

Abstract

Purpose Extracorporeal photopheresis (ECP) treatment following heart transplantation (HTx) may induce transplant tolerance. A monitoring tool for successful ECP treatment would allow determination of patient-specific duration and frequency of ECP therapy. We evaluated the immunological effects of ECP long-term therapy. Methods ECP therapy started 3 months after HTx (n=19). ECP therapy included a total of 5 cycles, each on 2 consecutive days every 4-8 wks over a mean period of 8.4±0.4 months. Blood samples were drawn prior to ECP (baseline), before each cycle and 4 months after the last cycle. Flow cytometry analysis of all samples specific subsets of both dendritic cells (DCs) and regulatory T cells (Tregs), which are involved in the immune tolerance response. Results Compared to baseline, ECP reduced CD4+ T cells (baseline: 23.2±9.2%, cycle 5: 23.6±3.4%, after ECP: 16.3±7.4%, p 0.01). DC subsets expressing blood dendritic cell antigen (BDCA) 1, 2, 3 or 4 increased during ECP but returned to baseline levels 4 months after ECP (BDCA1prior ECP: 42.1±13.4%, BDCA1cycle 5: 53.4±3.7%, BDCA1after ECP: 43.6±8.7%, BDCA2prior ECP: 20.2±9.1%, BDCA2cycle 5: 32.6±3.2%, BDCA2after ECP: 24.0±6.0%, BDCA3prior ECP: 73.2±17.8%, BDCA3cycle 5: 90.4±5.0%, BDCA3after ECP: 75.4±12.4%, BDCA4prior ECP: 21.6±10.0%, BDCA4cycle 5: 31.7±3.9%, BDCA4after ECP: 21.4±5.9%, all p≤0.01). Conclusion Our results suggest that a combined increase of BDCA1+, 2+, 3+ and 4+ DCs, total Tregs and the highly suppressive CD39+ Treg subset could be useful to monitor ECP therapy after HTx, and, to establish an individual ECP treatment schedule. Future studies need to explore ECP effects on immune cells in the context with clinical events like rejection or infection.