Induction of tolerance in a rat model of laryngeal transplantation.
BACKGROUND
The major limitation preventing expansion of laryngeal transplantation as a therapeutic modality is the necessity of lifelong immunosuppression. In this report, we describe an immunomodulatory strategy for tolerance induction in laryngeal allotransplantation that permits escape from chronic immunosuppression.


METHODS
Larynges were transplanted from Lewis-Brown-Norway (RT1l/n, F1) donors to Lewis (RT1l) recipients. Recipients received 7 days of treatment with tacrolimus and mouse anti-rat alphabeta T-cell-receptor (TCR) monoclonal antibodies. Histology, mixed lymphocyte reaction (MLR), skin grafting, and flow cytometry assessed functional tolerance, efficacy of immunodepletion, and donor-specific chimerism.


RESULTS
All 10 recipients survived until sacrifice at 100 days. Histology suggested functional allograft tolerance. Skin grafting, MLR, and flow cytometry revealed that tolerance is neither donor-specific nor related to systemic immunocompromise.


CONCLUSIONS
In this rat laryngeal-transplantation model, functional tolerance was induced under combined tacrolimus and alphabeta TCR protocol. Mechanisms responsible for this tolerance induction require future elucidation.
Akst
Lee M
LM
Department of Otolaryngology and Communicative Disorders,The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Siemionow
Maria
M
Dan
Olivia
O
Izycki
Dariusz
D
Strome
Marshall
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007830:Larynx / Q000637:transplantation*; D007959:Lymphocyte Culture Test, Mixed; D023421:Models, Animal; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D016559:Tacrolimus / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell; D016559:Tacrolimus