Postallograft donor and recipient dendritic cell trafficking in the rat larynx.
OBJECTIVE
Dendritic cells (DC) are potent antigen-presenting cells that instigate allograft rejection. Their migration kinetics vary depending on the type of organ transplanted. The timing of donor and recipient DC trafficking in laryngeal transplants is unknown.


METHODS
Prospective animal model.


METHODS
Lewis to Brown Norway (BN) rat laryngeal allografts and BN to BN isografts were performed without immunosuppression. Recipient animals were sacrificed at seven posttransplant time points. Total DC, as well as recipient and donor DC (in allograft recipients), were enumerated in situ in the airway epithelium and subepithelium using monoclonal antibodies, immunofluorescence, confocal microscopy, and image analysis software.


RESULTS
Total DC densities in both laryngeal allografts and isografts decreased to approximately 10% of their initial values in the first 3 days and then rose beyond their starting values. In allografts, there was a net efflux of donor DC, reaching a nadir by 3 to 5 days; they were identified in recipient cervical lymph nodes from 12 hours to 5 days. Recipient DC infiltrated the laryngeal allograft, reaching a maximal density by day 7.


CONCLUSIONS
The paradigm of donor DC efflux and recipient DC influx has been confirmed in a rat laryngeal transplant model, and the allograft-specific timing of these events has been elucidated. Similarities in total DC migration between allografts and isografts suggest that this phenomenon may not be driven entirely by major histocompatibility mismatch. Further understanding of trafficking may help with the goal of manipulating DC to induce allograft tolerance in the absence of generalized immunosuppression.
Friedman
Aaron D
AD
Head and Neck Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. friedma@ccf.org
Dan
Olivia
O
Drazba
Judith A
JA
Lorenz
Robert R
RR
Strome
Marshall
M
D000818:Animals; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D007830:Larynx / Q000276:immunology / Q000637:transplantation*; D008297:Male; D011446:Prospective Studies; D051381:Rats; D011917:Rats, Inbred Lew; D014019:Tissue Donors; D014180:Transplantation
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; C459465:OX-62 antigen, rat