Study of immunological mechanisms during successful withdrawal of immunosuppression after living donor liver transplantation

活体肝移植成功撤除免疫抑制过程中的免疫机制研究

• 批准号: 11470258
• 负责人: EGAWA Hiroto
• 金额: $ 7.3万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470258/
• 关键词: living donor liver transplantation; tolerance; immunosuppression withdrawal; humoral factors; cytokines; cellular factors; regulatory T cells; Tacrolimus; 免疫抑制剤; 計画的離脱; リンパ球混合試験; 非特異的免疫寛容; 免疫染色; アポトーシス; Fas-Fasリガンド; 免疫抑制; RT-PCR

This study aims to clarify the mechanisms of clinical tolerance, to identify indicators for safe withdrawal of immunosuppression, and to increase the number of patients free from immunosuppression. Patients free from immunosuppression after living liver transplantation (IS free patients) were investigated, such as Th1 & Th2 cytokines, regulatory T cells. 1) IS free patients showed donor specific hypo-response in MLR and the Th1 cytokines were down regulated in IS free patients compared with third party MLR. 2) There was no specific feature in cytokine gene expression in liver biopsy tissue in IS free patients. 3) The serum of IS free patients showed nonspecific suppression in MLR but we could not isolate and identify the substance yet. 4) The number of CD4+/CD25+ cells and γ/δ TCR+ T cells were increased in IS free patients compared with healthy people. 5) In clinical, over 900 patients underwent living donor liver transplantation in our institution and the number of patients completely free from immunosuppression was increased from 15 in 1998 to 49 in 2002 and other 36 patients were under weaning protocol. We continue to study cellar factors as the most possible indicators for IS withdrawal.

本研究旨在阐明临床耐受的机制，确定安全停用免疫抑制剂的指标，并增加免于免疫抑制的患者数量。对活体肝移植术后无免疫抑制的患者（IS free patients，IS free patients）进行Th 1、Th 2细胞因子、调节性T细胞的检测。1)与第三方MLR相比，无IS患者在MLR中表现出供者特异性低反应，Th 1细胞因子在无IS患者中下调。2)无IS患者肝活检组织细胞因子基因表达无特异性。3)无IS患者血清对MLR有非特异性抑制作用，但尚不能分离鉴定。4)与健康人相比，无IS患者外周血中CD 4 +/CD 25+细胞和γ/δ TCR+ T细胞数量增加。5)临床上，我院共完成活体肝移植900余例，完全解除免疫抑制者由1998年的15例增加到2002年的49例，另有36例处于脱机状态。我们继续研究地窖因素作为IS撤退的最可能指标。

项目成果

Koichi Tanaka: "Current status of living donor liver transplantation in adults"Current Opinion in Organ Transplantation. 5・2. 74-79 (2000)

田中浩一：“成人活体肝移植的现状”《器官移植现状》5・2（2000）。

上本伸二: "小児生体部分肝移植"臨床外科. 55・1. 55-59 (2000)

植本慎司：“小儿活体部分肝移植”临床外科55・1（2000）。

猪股裕紀洋: "生体肝移植における免疫抑制離脱"日本臨床免疫学会会誌. 22(6). 431-435 (1999)

Yukihiro Inomata：“活体肝移植中免疫抑制的撤消”，日本临床免疫学会杂志 22(6) (1999)。

Sachiko Minamiguchi: "Living related liver transplantation: Histopathologic analysisi of graft dysfunction in 304 patients"Human Pathology. 30(12). 1479-1487 (1999)

Sachiko Minamiguchi：“活体相关肝移植：304 例患者移植物功能障碍的组织病理学分析”《人类病理学》。

T. Hashida, S. Masuda, S. Uemoto, H. Saito, K. Tanaka, K. Inui: "Pharmacokineric and prognostic significance of intestinal MDRI expression in recipients of living-donor liver transplantation"Clinical Pharmacology & Therapeutics. 69. 308-316 (2001)

T. Hashida、S. Masuda、S. Uemoto、H. Saito、K. Tanaka、K. Inui：“活体肝移植受者肠道 MDRI 表达的药代动力学和预后意义”临床药理学