Induction of donor specific unresponsiveness by combined treatment with donor bone marrow cell infusion, and FK506 in cadaveric renal allotransplantation.

在尸体肾同种异体移植中，通过与供体骨髓细胞输注和 FK506 联合治疗诱导供体特异性无反应。

• 批准号: 04670748
• 负责人: WATANABE Koji
• 金额: $ 0.96万
• 依托单位: Department of Immunology, Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670748/
• 关键词: Preserved kidney; Kidney allografting; DLA-DNA typing; FK506; Bone marrow cells; Lymphoid irradiation; 全リンパ組織選択的照射法; Donor骨髄細胞移植

We succeeded in the prolongation of skin and kidney allografts from bone marrow donors in histoincompatible beagle dogs by combined treatment with preoperative fractionated lymphoid irradiation (FLI) , bone marrow cell (BMC) infusion from the kidney donors shortly before kidney grafting, and shortterm administration of small doses of immunosuppressant, FK506. To apply this protocol to the cadaveric renal transplantation, we have investigated the several points as fllows ; First, we established the DLA-DNA typing using ll SSO probes by the method of PCR-SSO typing by which the same DLA mismatched pairs were obtained. Second, the results of allografting of 3-days preserved kidneys was remarkably improved by extensively cooling the transplants with ice-water system made by ourselves until revascularization in the course of operation. Third, we adapted the postoperative immunosuppression as follows ; i.m.administration of FK506 at the dose of 0.16mg/kg/d for 14 days, followed by 0.08mg/kg/d for 14 days, then continued to give the dose of 0.04mg/kg/d until 90 days postoperatively. In fact, by these treatment the survival rate of allografted preserved kidneys have been greatly improved. Then, the effect of combined treatment with FLI,and, BMC infusion at the time of grafting has been under investigation.

我们成功地延长了组织不合的Beagle犬的同种异体皮肤和肾移植，方法是联合应用术前分次淋巴照射(FLI)、肾移植前供者的骨髓细胞(BMC)输注和短期应用小剂量免疫抑制剂FK506。为了将该方法应用于身体肾移植，我们对以下几个方面进行了研究：首先，我们用11个SSO探针通过PCR-SSO分型的方法建立了DLA-DNA分型，获得了相同的DLA错配对。采用自制冰水系统广泛降温，直至术中血运重建，可显著提高保存3天的同种异体肾移植效果。术后免疫抑制调整如下：FK506静脉注射0.16 mg/kg/d，连续14天，然后0.08 mg/kg/d，连续14天，然后继续给予0.04 mg/kg/d，直至术后90天。事实上，通过这些治疗，保存的同种异体肾脏的存活率已经大大提高。然后，对移植时联合应用FLI和BMC输注的效果进行了观察。

项目成果

伊東一郎他.: "北里自家繁殖mongrel犬の主要組織適合抗原(DLA)DRB1遺伝子の解析." MHC & IRS(日本組織適合性学会誌). 1. 115- (1994)

Ito 等人：“北里家养杂种狗主要组织相容性抗原 (DLA) DRB1 基因的分析。”MHC & IRS（日本组织相容性学会杂志）1. 115-（1994）。

K.Watanabe, I.Ito, F.Otani, F.Obata, K.Sato, K.Ishida, Y.Masaki, S.Maruyama, and K.Kashiwagi: "Factors influencing long-term operational tolerance in dogs treated with fractionated lymphoid irradiation, donor bone marrow cell infusion and FK506." Transpla

K.Watanabe、I.Ito、F.Otani、F.Obata、K.Sato、K.Ishida、Y.Masaki、S.Maruyama 和 K.Kashiwagi：“影响分次治疗犬长期操作耐受性的因素

K.Watanabe, I.Ichiro, K.Sato, K.Ishida, Y.Nakayama, A.Kakita, and Y.Masaki.: "Induction of transplatation tolerance by donor bone marrow transplantation in adult beagle dogs." J.Jpn.Surg.Soc. (Japanese). 95. 301 (1994)

K.Watanabe、I.Ichiro、K.Sato、K.Ishida、Y.Nakayama、A.Kakita 和 Y.Masaki.：“通过成年比格犬供体骨髓移植诱导移植耐受。”

大谷文雄 他: "イヌMHC(DLA)のPCR・SSO法によるタイピングと新しい抗原型の発見" 第2回日本組織適合性学会大会. 抄録集. 72 (1993)

Fumio Otani 等人：“通过 PCR/SSO 方法对狗 MHC (DLA) 进行分型并发现新的抗原类型”，日本组织相容性协会第二届年会摘要 (1993)。

渡部浩二他.: "成犬において導入した同種移植片に対する免寛容の機序" 日本免疫学会総会・学術集会記録.22. 301 (1992)

Koji Watanabe 等：“成年狗对引入同种异体移植物的耐受机制”日本免疫学会大会和学术会议记录 22. 301 (1992)