Tchervenkov J I, Cofer B R, Davies C, Alexander J W
Department of Surgery, University of Cincinnati Medical Center, Ohio 45267-0558, USA.
Transplantation. 1995 Mar 27;59(6):821-4.
A single donor specific transfusion (DST) 24 hr pretransplant and Cyclosporine (CsA) are synergistic in inducing prolongation of allograft survival. This synergy was further potentiated by giving 3 additional DSTs at weekly intervals posttransplant, or by the additional administration of a small dose of the anti-T cell monoclonal antibody OX-52 24 hr pretransplant to the above protocol. This study determined whether indefinite survival can be achieved in the ACI-to-Lewis heart allograft model by combining an anti-T cell monoclonal antibody, 4 DSTs given once 24 hr pretransplant and weekly 3 times posttransplant, and CsA. CsA was given daily for 28 days or 60 days posttransplant. The dose consisted of CsA 5 mg/kg/day starting 24 hr pretransplant and continuing until day 7 posttransplant and followed by 2.5 mg/kg/day for either 21 more days (total CsA days = 28 days) or 53 days (total CsA days = 60 days). The anti-T cell monoclonal antibody OX52 (200 micrograms i.v.) was given once 24 hr pretransplant. DST (1 ml) was given 24 hr pretransplant and on days 7, 14, and 21 posttransplant. Low-dose CsA for 28 days never induced indefinite allograft survival. CsA for 60 days, however, resulted in the occasional indefinite allograft survival (> 1 year) even in this difficult model. The addition of DST 24 hr pre- and posttransplant on days 7, 14, and 21 to both 28 days and 60 days of CsA further prolonged allograft survival. The best survival was seen in the group given DST 24 hr pre- and on days 7, 14, and 21 posttransplant and 60 days of CsA, with all the allografts surviving beyond 100 days of CsA, with all the allografts surviving beyond 100 days and more than 50% surviving indefinitely (> 1 year). The addition of a single dose of OX52 24 hr pretransplant to the multiple DSTs and 28 days of CsA protocol significantly improved indefinite allograft survival but its influence was less dramatic when given to the multiple DSTs and 60 days of CsA protocol. This beneficial interaction between CsA, DST, and an anti-T cell MoAb offers a clinically applicable protocol for both living donor and cadaveric organ transplantation in inducing donor-specific hyporesponsiveness, and further investigations are warranted.
移植前24小时进行单次供体特异性输血（DST）与环孢素（CsA）在诱导同种异体移植物存活期延长方面具有协同作用。在移植后每周额外进行3次DST，或者在上述方案基础上于移植前24小时额外给予小剂量抗T细胞单克隆抗体OX - 52，可进一步增强这种协同作用。本研究确定了在ACI到Lewis心脏同种异体移植模型中，通过联合使用抗T细胞单克隆抗体、移植前24小时给予1次及移植后每周3次共给予4次DST以及CsA，是否能够实现无限期存活。移植后CsA每日给药，持续28天或60天。剂量为移植前24小时开始给予CsA 5mg/kg/天，持续至移植后第7天，随后给予2.5mg/kg/天，再持续21天（CsA总给药天数 = 28天）或53天（CsA总给药天数 = 60天）。抗T细胞单克隆抗体OX52（静脉注射200微克）在移植前24小时给药1次。DST（1ml）在移植前24小时以及移植后第7、14和21天给药。28天的低剂量CsA从未诱导出无限期的同种异体移植物存活。然而，即使在这个困难的模型中，60天的CsA治疗也偶尔会导致同种异体移植物无限期存活（>1年）。在28天和60天的CsA治疗方案基础上，于移植前24小时以及移植后第7、14和21天添加DST，可进一步延长同种异体移植物存活期。在移植前24小时以及移植后第7、14和21天给予DST并进行60天CsA治疗的组中观察到最佳存活情况，所有同种异体移植物在CsA治疗100天后仍存活，所有同种异体移植物存活超过100天，且超过50%无限期存活（>1年）。在多次DST和28天CsA方案中，移植前24小时添加单剂量OX52可显著提高同种异体移植物无限期存活，但在多次DST和60天CsA方案中给予时，其影响较小。CsA、DST和抗T细胞单克隆抗体之间的这种有益相互作用为活体供体和尸体器官移植提供了一种临床适用的方案，可诱导供体特异性低反应性，值得进一步研究。
