Sharabi Y, Aksentijevich I, Sundt T M, Sachs D H, Sykes M
Transplantation Biology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Exp Med. 1990 Jul 1;172(1):195-202. doi: 10.1084/jem.172.1.195.
The development of safe methods for inducing donor-specific tolerance across xenogeneic barriers could potentially relieve the critical shortage of allograft donors that currently limits the applicability of organ transplantation. We report here that such tolerance can be induced in a xenogeneic combination (rat----mouse) using a nonmyeloablative and nonlethal preparative regimen. Successful induction of chimerism and donor-specific transplantation tolerance required pretreatment of recipients with monoclonal antibodies (mAbs) against NK1.1, Thy-1.2, CD4 and CD8, followed by administration of 3 Gy whole body radiation (WBI), 7 Gy thymic irradiation, and infusion of T cell-depleted rat bone marrow cells (BMC). Rat cells appeared among peripheral blood lymphocytes (PBL) of such recipients by 2-3 wk, and rat T cells by 2-5 wk following bone marrow transplantation (BMT). Donor-type rat skin grafts placed 4 mo after BMT were accepted, while simultaneously placed non-donor-type rat skin grafts were promptly rejected. In addition to its clinical potential, the ability to induce donor-specific tolerance across xenogeneic barriers using such a nonlethal preparative regimen provides a valuable model for the study of mechanisms of xenogeneic transplantation tolerance.
开发跨越异种屏障诱导供体特异性耐受的安全方法，可能会缓解目前限制器官移植适用性的同种异体移植供体严重短缺的问题。我们在此报告，使用非清髓性和非致死性预处理方案，可在异种组合（大鼠→小鼠）中诱导出这种耐受性。成功诱导嵌合体形成和供体特异性移植耐受需要先用抗NK1.1、Thy-1.2、CD4和CD8的单克隆抗体（mAb）对受体进行预处理，然后进行3 Gy全身照射（WBI）、7 Gy胸腺照射，并输注去除T细胞的大鼠骨髓细胞（BMC）。在骨髓移植（BMT）后2至3周，此类受体的外周血淋巴细胞（PBL）中出现大鼠细胞，2至5周后出现大鼠T细胞。BMT后4个月植入的供体型大鼠皮肤移植物被接受，而同时植入的非供体型大鼠皮肤移植物则迅速被排斥。除了其临床潜力外，使用这种非致死性预处理方案跨越异种屏障诱导供体特异性耐受的能力，为研究异种移植耐受机制提供了一个有价值的模型。
