Sheffield C D, Hadley G A, Dirden B M, Bartlett S T
Department of Surgery, University of Maryland Medical Systems, Baltimore 21201.
J Surg Res. 1994 Jul;57(1):55-9.
The shortage of suitable human organs currently limits widespread utilization of clinical transplantation. Successful xenotransplantation could potentially eliminate the shortage of suitable organs for transplantation. The present study determines the effect of intrathymic donor spleen cell injection on the survival of cardiac xenografts performed without post-transplant immunosuppression. Wistar-Furth rats served as recipients of Lewis rat cardiac allografts or Golden Syrian hamster cardiac xenografts either with or without intrathymic donor spleen cell injection. Some xenograft cohorts were pretreated with four doses of cyclophosphamide prior to cardiac transplantation. Graft function was assessed by daily graft palpation and rejection was defined as cessation of graft function. Cardiac allograft median survival time (MST) was 8 days in untreated recipients. Pretreatment with intrathymic donor spleen cell injection led to essentially indefinite allograft survival (MST > 100 days). Control xenograft survival was 3 days with no significant prolongation seen when intrathymic donor spleen cell injection was performed (MST = 2.5 days). The addition of pulse-dose cyclophosphamide resulted in markedly prolonged xenograft survival (MST = 30 days) compared to control (P < 0.01) and to cyclophosphamide alone (MST = 9.5 days, P < 0.01). Cardiac xenografts undergo a vigorous rapid rejection. The time course of rejection was not altered by the intrathymic presence of donor cells under conditions which lead to indefinite survival of cardiac allografts. A brief period of pretransplant cyclophosphamide treatment markedly improved the success of the thymic tolerance protocol in xenografts. This finding suggests that temporary inhibition of humoral immunity may be permissive for the development of thymic tolerance to cell-mediated immunity in xenotransplants.
目前，合适的人体器官短缺限制了临床移植的广泛应用。成功的异种移植有可能消除合适移植器官的短缺。本研究确定胸腺内注射供体脾细胞对在无移植后免疫抑制情况下进行的心脏异种移植存活的影响。Wistar-Furth大鼠作为Lewis大鼠心脏同种异体移植或金黄叙利亚仓鼠心脏异种移植的受体，分别接受或不接受胸腺内注射供体脾细胞。部分异种移植组在心脏移植前用四剂环磷酰胺进行预处理。通过每日触诊移植心脏评估移植物功能，将移植功能停止定义为排斥反应。未治疗的受体中，心脏同种异体移植的中位存活时间（MST）为8天。胸腺内注射供体脾细胞预处理导致同种异体移植基本无限期存活（MST>100天）。对照异种移植存活时间为3天，进行胸腺内注射供体脾细胞时未见明显延长（MST = 2.5天）。与对照组（P<0.01）和单独使用环磷酰胺组（MST = 9.5天，P<0.01）相比，脉冲剂量环磷酰胺的加入使异种移植存活时间显著延长（MST = 30天）。心脏异种移植会经历强烈的快速排斥反应。在导致心脏同种异体移植无限期存活的条件下，胸腺内存在供体细胞并未改变排斥反应的时间进程。移植前短期使用环磷酰胺治疗显著提高了异种移植中胸腺耐受方案的成功率。这一发现表明，暂时抑制体液免疫可能有利于异种移植中对细胞介导免疫产生胸腺耐受。
