Sato Yoshinobu, Ichida Takafumi, Watanabe Hisami, Yamamoto Satoshi, Abo Toru, Hatakeyama Katsuyoshi
First Department of Surgery, Niigata University School of Medicine, 1-757 Asahimachi-dori, Niigata 951-8510, Japan.
Hepatogastroenterology. 2003 Nov-Dec;50(54):2161-5.
Antigens given orally or through the portal vein are known to be less immunogenic and to induce immunologic unresponsiveness. The mechanisms responsible for graft enhancement are still unclear. Moreover, in actuality, it is difficult to perform transfer of donor antigens via the portal vein in clinical transplantation. We investigated the effect of transfer of donor blood via the portal vein intra- and post-operatively in living related donor liver transplantation for recurrent multiple hepatocellular carcinoma. A 62-year-old female, who suffered from recurrent multiple hepatocellular carcinoma with hepatitis C virus, underwent living related donor liver transplantation with the right lobe of her daughter. Eleven hepatocellular carcinomas were recognized in the resected specimen. Donor blood was administered via the portal vein using a catheter inserted in the middle colic vein intra- and postoperatively. Mononuclear cells were obtained by operative liver biopsy or postoperative biopsy using fine needle aspiration biopsy, and from peripheral blood. They were analyzed by two or three color-flow cytometry using several antibodies. The differentiation between donor and recipient was estimated by means of anti-HLA antibodies of donor and recipient. The postoperative course was uneventful. She did not suffer from acute cellular rejection and was discharged on day 30 the after operation. CD56+ CD3+ T cells in the liver increased notably from 20% to 50% after transplantation. One half of the CD56+ CD3+ T cells in the liver graft were of the donor type (donor anti-HLA A2 antibody) on day 8 after surgery. Donor type CD56+ CD3+ T cells occupied 17.4% of the total CD56+ CD3+ T cells even on day 42 after the operation. Stimulation index by mixed lymphocyte reaction continued at a low level (< 2) from day 1 after the operation. Steroids were discontinued after 40 postoperative days. FK506 was also reduced to 0.5 mg/day 4 months after the operation. There was no recurrence of hepatocellular carcinoma and hepatitis C virus for two years after the operation. Macrochimerism of donor type CD56+ CD3+ T cells in a graft might be induced by the transfer of donor blood via the portal vein and may play an important role in transplantation tolerance. Inoculation of donor blood via the portal vein may also be very useful for rapid reduction of immunosuppression.
口服或经门静脉给予的抗原已知免疫原性较低，并会诱导免疫无反应性。导致移植物增强的机制仍不清楚。此外，在实际临床移植中，通过门静脉进行供体抗原转移很困难。我们研究了在亲属活体供肝移植治疗复发性多发性肝细胞癌术中及术后经门静脉输注供体血液的效果。一名62岁患有复发性多发性肝细胞癌合并丙型肝炎病毒的女性，接受了其女儿右叶的亲属活体供肝移植。在切除的标本中发现了11个肝细胞癌。术中及术后通过插入中结肠静脉的导管经门静脉输注供体血液。通过手术肝活检或术后细针穿刺活检以及外周血获取单核细胞。使用多种抗体通过两色或三色流式细胞术对其进行分析。通过供体和受体的抗HLA抗体评估供体和受体之间的差异。术后过程顺利。她未发生急性细胞排斥反应，术后第30天出院。移植后肝脏中CD56+CD3+T细胞显著增加，从20%升至50%。术后第8天，肝移植中一半的CD56+CD3+T细胞为供体型（供体抗HLA A2抗体）。即使在术后第42天，供体型CD56+CD3+T细胞仍占总CD56+CD3+T细胞的17.4%。术后第1天起，混合淋巴细胞反应的刺激指数持续处于低水平（<2）。术后40天后停用类固醇。术后4个月，FK506也减至0.5mg/天。术后两年未出现肝细胞癌复发及丙型肝炎病毒复发。经门静脉输注供体血液可能诱导移植物中供体型CD56+CD3+T细胞的大嵌合现象，并可能在移植耐受中发挥重要作用。经门静脉接种供体血液对于快速降低免疫抑制也可能非常有用。
