Induction of tolerance in a rat model of laryngeal transplantation

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 immunosu...

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Veröffentlicht in:Transplantation 2003-12, Vol.76 (12), p.1763-1766
Hauptverfasser: AKST, Lee M, SIEMIONOW, Maria, DAN, Olivia, IZYCKI, Dariusz, STROME, Marshall
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container_end_page 1766
container_issue 12
container_start_page 1763
container_title Transplantation
container_volume 76
creator AKST, Lee M
SIEMIONOW, Maria
DAN, Olivia
IZYCKI, Dariusz
STROME, Marshall
description 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. 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. 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. 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.
doi_str_mv 10.1097/01.TP.0000100398.39169.5B
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source MEDLINE; Journals@Ovid Complete
subjects Animals
Antibodies, Monoclonal - therapeutic use
Biological and medical sciences
Combined surgery. Multiple transplantations
Graft Survival - drug effects
Graft Survival - immunology
Immunosuppression - methods
Immunosuppressive Agents - therapeutic use
Larynx - transplantation
Lymphocyte Culture Test, Mixed
Medical sciences
Models, Animal
Rats
Rats, Inbred BN
Rats, Inbred Lew
Receptors, Antigen, T-Cell - immunology
Skin Transplantation - immunology
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Tacrolimus - therapeutic use
Transplantation Conditioning - methods
Transplantation, Homologous - immunology
title Induction of tolerance in a rat model of laryngeal transplantation
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