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.
Kofler
Sieglinde
S
Medizinische Klinik und Poliklinik I, University Medical Center Munich-Grosshadern, Ludwig-Maximilians University of Munich, Munich, Germany.
Petrakopoulou
Paraskevi
P
Grimm
Cornelia
C
Kaczmarek
Ingo
I
Meiser
Bruno M
BM
Weis
Michael
M
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000000981:diagnostic imaging / Q000473:pathology; D016027:Heart Transplantation; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D037181:Lectins, C-Type / Q000378:metabolism; D008833:Microcirculation; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D010496:Pericardium / Q000503:physiopathology; D011184:Postoperative Period; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000378:metabolism; D013601:T-Lymphocytes / Q000473:pathology; D013997:Time Factors; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000000981:diagnostic imaging; D018084:Ultrasonography, Interventional; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin