Akst Lee M, Siemionow Maria, Dan Olivia, Izycki Dariusz, Strome Marshall
Department of Otolaryngology and Communicative Disorders,The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Transplantation. 2003 Dec 27;76(12):1763-70. doi: 10.1097/01.TP.0000100398.39169.5B.
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.
阻碍喉移植作为一种治疗方式广泛应用的主要限制因素是需要终身免疫抑制。在本报告中，我们描述了一种在喉同种异体移植中诱导免疫耐受的免疫调节策略，该策略可避免长期免疫抑制。
将喉从Lewis-Brown-Norway（RT1l/n，F1）供体移植到Lewis（RT1l）受体。受体接受了7天的他克莫司和小鼠抗大鼠αβT细胞受体（TCR）单克隆抗体治疗。通过组织学、混合淋巴细胞反应（MLR）、皮肤移植和流式细胞术评估功能耐受、免疫清除效果和供体特异性嵌合体。
所有10只受体均存活至100天时处死。组织学显示同种异体移植物具有功能耐受。皮肤移植、MLR和流式细胞术表明，耐受既不是供体特异性的，也与全身免疫抑制无关。
在该大鼠喉移植模型中，联合应用他克莫司和αβTCR方案可诱导功能耐受。这种耐受诱导的机制有待进一步阐明。
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