TY - JOUR
T1 - Induction of tolerance in a rat model of laryngeal transplantation
AU - Akst, Lee M.
AU - Siemionow, Maria
AU - Dan, Olivia
AU - Izycki, Dariusz
AU - Strome, Marshall
PY - 2003/12/27
Y1 - 2003/12/27
N2 - 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. Materials and Methods. Larynges were transplanted from Lewis-Brown-Norway (RT11/n, F1) donors to Lewis (RT1 1) recipients. Recipients received 7 days of treatment with tacrolimus and mouse anti-rat αβ 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 αβ TCR protocol. Mechanisms responsible for this tolerance induction require future elucidation.
AB - 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. Materials and Methods. Larynges were transplanted from Lewis-Brown-Norway (RT11/n, F1) donors to Lewis (RT1 1) recipients. Recipients received 7 days of treatment with tacrolimus and mouse anti-rat αβ 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 αβ TCR protocol. Mechanisms responsible for this tolerance induction require future elucidation.
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U2 - 10.1097/01.TP.0000100398.39169.5B
DO - 10.1097/01.TP.0000100398.39169.5B
M3 - Article
C2 - 14688529
AN - SCOPUS:0347993685
SN - 0041-1337
VL - 76
SP - 1763
EP - 1766
JO - Transplantation
JF - Transplantation
IS - 12
ER -