Bootcongres

Background and Methods: Monocyte-macrophage lineage cells are key players in graft rejection and tolerance. To investigate whether local events in transplanted hearts are reflected in the circulating monocyte population, we investigated in 10 heart transplant recipients the monocyte subset composition and their phenotypic and functional characteristics at rejection vs. no rejection time points by flowcytometry. The rejection status was determined by transplant biopsy analysis. In addition, using a cross-sectional approach, we compared the monocyte kinetics in heart transplant recipients with a cohort of 33 healthy individuals. Results: Comparing the monocyte subsets from heart transplant recipients with those from healthy individuals, we observed an increased percentage of the CD14++16- classical monocytes and a simultaneous decrease in the percentage of CD14++16+ intermediate and CD14+16++ non-classical monocytes. However, no intra-individual differences were observed between rejection and non-rejection time points. After stimulation of monocytes with both LPS, and with MLR-activated donor-derived spleen cells, the capacity to produce TNF-α, IFN-γ, IL-1β, IL-6, and IL-10 was consistently high in heart transplant recipients, independent of rejection status, and comparable to healthy individuals. Increased HLA-DR expression was observed in heart transplant recipients compared to healthy individuals in all monocyte subsets indicative of a higher potential for antigen presentation. HLA-DR expression on CD16+ monocytes was even more increased during rejection compared to non-rejection time points. 

Conclusion: Increased percentage of CD14++16- classical monocytes and decreased percentages of CD14++16+ intermediate and CD14+16++ non-classical monocytes signify the monocyte kinetics in heart transplant recipients as compared to healthy individuals. We observed no differences in monocyte subset composition at rejection compared with non-rejection. Remarkably, despite the immunosuppressive drugs, the monocyte-derived cytokine production in heart transplant recipients was consistently high and comparable with healthy individuals.