Graft-infiltrating Dendritic Cells and Coronary Endothelial Dysfunction After Human Heart Transplantation

Background Indirect allorecognition is involved in chronic transplant rejection. We prospectively characterized graft-infiltrating dendritic cells (DCs) in sequential myocardial biopsies ( n = 64; 1 to 24 months after transplantation) from 16 patients after heart transplantation (HTx) and analyzed the relation between graft immune activation and structural and functional coronary changes during follow-up. Methods DC invasion (immunostaining) in the human myocardium was detectable early after HTx, increased further during the first year, and decreased constantly thereafter. Also, graft-infiltrating DCs expressed markers of immaturity and maturity and were time-dependently clustered with CD3-positive T cells. Results Both epicardial and microvascular endothelial dysfunction were associated with elevated CD209-positive DCs at 12 months. CD209 positivity early after HTx was an independent marker for coronary endothelial dysfunction during follow-up. Intimal hyperplasia or angiographic disease during follow-up was not associated with myocardial DC infiltration. Conclusions DCs frequently infiltrate the cardiac allograft with a peak during the first post-operative year and time-dependently cluster with T cells. Migratory active graft-infiltrating DCs may serve as a predictor for allograft coronary endothelial dysfunction.