Valdivia L A, Monden M, Gotoh M, Tono T, Nakano Y, Mori T
Department of Surgery II, Osaka University Medical School, Japan.
Transplantation. 1991 Oct;52(4):594-9. doi: 10.1097/00007890-199110000-00003.
The effect of donor-specific blood transfusion (DST), in combination with pretransplant immunosuppression with deoxyspergualin (DSG), on hamster-to-Wistar rat cardiac xenograft survival was assessed. While DST given on day -6 sensitized the recipients, resulting in hyperacute xenograft rejection, the addition of 5 mg/kg/k/day DSG from the day of transfusion to the day of grafting not only prevented hyperacute rejection but resulted in prolongation of graft survival from 3.4 +/- 0.5 days in untreated controls to 7.0 +/- 0.7 days (P less than 0.01). In contrast, DSG alone as pretransplant immunosuppression had no beneficial effect and rejection occurred in 4.0 +/- 0.7 days. This effect appears to be at least donor species-specific, in the sense that ACI cardiac allograft survival was not prolonged when transplanted into xenotransfused and DSG-treated Wistar recipients. DST alone resulted in marked increase in antibody titers, showing the value of 1:512 or more on transplantation day. On the other hand, combined treatment suppressed the titers to 1:1-1:4 on that day. An adoptive cell transfer system was used to analyze the mechanisms underlying this effect. When sublethally irradiated secondary hosts were transferred with 5 x 10(7) lymph node cells (LNCs) harvested on day 0 from xenotransfused and DSG-treated rats, the test heart xenograft survived longer than the irradiated and nontransferred controls, suggesting the presence of suppressor cells. Further in vitro studies demonstrate that LNCs from DST+DSG-treated rats response less in a mixed lymphocyte reaction to hamster LNCs (41% on day 0 [P less than 0.01]), compared with the controls. In coculture experiments, the LNCs from treated recipients suppressed the response of unmodified Wistar LNCs to hamster LNCs by 76% on day 0 compared with the positive controls (P less than 0.01). On the other hand, the transfer of serum taken from treated rats on day 0 did not lead to prolongation of test heart xenografts in syngeneic naive hosts. These findings suggest that the mechanisms underlying the hyporesponsiveness induced by pretreatment with DST and DSG include the induction of suppressor cells, although a degree of clonal deletion can not be ruled out. The generation of serum suppressor factors seems to have no role in this phenomenon.
评估了供者特异性输血（DST）联合移植前用去氧精胍菌素（DSG）进行免疫抑制对仓鼠到Wistar大鼠心脏异种移植存活的影响。虽然在第-6天给予DST会使受体致敏，导致超急性异种移植排斥反应，但从输血当天到移植当天添加5mg/kg/k/天的DSG不仅可预防超急性排斥反应，还能使移植物存活时间从未治疗对照组的3.4±0.5天延长至7.0±0.7天（P<0.01）。相比之下，单独使用DSG作为移植前免疫抑制没有有益效果，排斥反应在4.0±0.7天发生。这种效应似乎至少具有供者物种特异性，即当将ACI心脏同种异体移植物移植到经异种输血和DSG处理的Wistar受体中时，其存活时间并未延长。单独的DST导致抗体滴度显著增加，在移植当天显示滴度值为1:512或更高。另一方面，联合治疗在当天将滴度抑制至1:1 - 1:4。采用过继性细胞转移系统分析这种效应的潜在机制。当对亚致死剂量照射的二级宿主输入从经异种输血和DSG处理的大鼠在第0天收获的5×10⁷个淋巴结细胞（LNC）时，受试心脏异种移植物的存活时间比照射但未转移的对照组更长，提示存在抑制细胞。进一步的体外研究表明，与对照组相比，来自DST + DSG处理大鼠的LNC在混合淋巴细胞反应中对仓鼠LNC的反应性更低（第0天为41%[P<0.01]）。在共培养实验中，与阳性对照组相比，来自处理受体的LNC在第0天可将未处理的Wistar LNC对仓鼠LNC的反应性抑制76%（P<0.01）。另一方面，在第0天从处理大鼠采集的血清转移至同基因未致敏宿主中并未导致受试心脏异种移植物存活时间延长。这些发现提示，DST和DSG预处理诱导低反应性的潜在机制包括抑制细胞的诱导，尽管不能排除一定程度的克隆清除。血清抑制因子的产生似乎在这一现象中不起作用。
