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

Research Project

Project/Area Number 11470258
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

EGAWA Hiroto  Kyoto University Transplant Surgery Associate Professor, 医学研究科, 助教授 (40293865)

Co-Investigator(Kenkyū-buntansha) UEMOTO Shinji  Mie University Surgery Professor, 医学部, 教授 (40252449)
INOMATA Yukihiro  Kumamoto University Pediatric Surgery Professor, 医学部, 教授 (50193628)
TANAKA Koichi  Kyoto University Transplant Surgery Professor, 医学研究科, 教授 (20115877)
KIUCHI Tetsuya  Nagoya University Transplant Surgery Professor, 医学研究科, 教授 (40303820)
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1999: ¥5,700,000 (Direct Cost: ¥5,700,000)
Keywordsliving 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
Research Abstract

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.

Report

(5 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (62 results)

All Other

All Publications (62 results)

  • [Publications] M.Kasahara et al.: "Postoperative flow cytometry crossmatch in Living donor liver transplantation"Transplantation. 67(4). 568-575 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Masuda et al.: "Effect of intestinal P-glycoprotein on daily tacrolimus trough level in a living-donor small bowel recipient"Clinical Pharmacology & Therapeutics. 68. 99-103 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Takatuki et al.: "Analysis of alloreactivity and intragraft cytokine profiles in living donor liver transplant recipients with graft acceptance"Transplant Immunology. 8. 279-286 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Hashida et al.: "Pharmacokineric and prognostic significance of intestinal MDRI expression in recipients of living-donor liver transplantation"Clinical Pharmacology & Therapeutics. 69. 308-316 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Takakura et al.: "Clinical implications of flow cytometry crossmatch with T or B cells in living donor liver transplantation"Clinical Transplantation. 15. 309-316 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Takatsuki et al.: "Weaning of immunosuppression in living donor liver transplant recipients"Transplantation. 72. 449-454 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Kiuchi et al.: "Clinical Transplats Chapter 18"Living Donor Liver Transplantation In Kyoto, 2001. 195-201 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Shimamura et al.: "Roles of the jejunum and ileum in the first-pass effect as absorptive barriers for orally administered tacrolimus"Journal of Surgical Research. 103(2). 215-222 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Matsukura et al.: "Significance of serial real-time pcr monitoring of ebv genome load in living donor liver transplantaiton"Clinical Transplantation. 16. 107-112 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Tanaka et al.: "Living-donor liver transplantation in the new decade : perspective from the twentieth to the twenty-first century"Journal of Hepatobiriary Pancreat Surg. 9. 218-222 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Goto et al.: "C3435T polymorphism in the Mdr1 gene affects the enterocyte expression level of Cyp3a4 rather than Pgp in recipients of living-donor liver transplantation"Parmacogenetics. 12. 451-457 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 田中紘一 他: "マイクロキメリズムと臓器移植"Immunology Frontier. 10. 35-39 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 尾池文隆 他: "生体肝移植における臨床的免疫寛容"今日の移植. 15(4). 358-361 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 上田幹子 他: "肝移植"小児科学 第2版. 189-191 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 上田幹子 他: "肝移植の長期予後"小児科. 43(11). 1652-1656 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 江川裕人 他: "我が国における臓器移植患者の予後;肝移植ICUとCCU"26. 919-926 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Kasahara, T. Kiuchi, K. Takakura, K. Uryuuhara, H. Egawa, K. Asonuma, S. Uemoto, Y. Inomata, S. Owada, Y. Morikawa, K. Tanaka: "Postoperative flow cytometry crossmatch in Living donor liver transplantation"Transplantation. 67(4). 568-575 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S. Masuda, S. Uemoto, T. Hashida, Y. Inomata, K. Tanaka, K. Inui: "Effect of intestinal P-glycoprotein on daily tacrolimus trough level in a living-donor small bowel recipient"Clinical Pharmacology & Therapeutics. 68. 99-103 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Takatuki, S. Uemoto, Y. Inomata, S. Sakamoto, M. Hayashi, M. Ueda, T. Kanematsu, K. Tanaka: "Analysis of alloreactivity and intragraft cytokine profiles in living donor liver transplant recipients with graft acceptance"Transplant Immunology. 8. 279-286 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Takakura, T. Kiuchi, M. Kasahara, K. Uryhara, S. Uemoto, Y. Inomata, K. Tanaka: "Clinical implications of flow cytometry crossmatch with T or B cells in living donor liver transplantation"Clinical Transplantation. 15. 309-316 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Takatsuki, S. Uemoto, Y. Inomata, H. Egawa, T. Kiuchi, S. Fujita, M. Hayashi, T. Kanematsu, K. Tanaka: "Weaning of irnmunosuppression in living donor liver transplant recipients"Transplantation. 72. 449-454 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Shimamura, S. Masuda, H. Saito, S. Sakamoto, S. Uemoto, K. Tanaka, K. Inui: "Roles of the jejunum and ileum in the first-pass effect as absorptive barriers for orally administered tacrolimus"Journal of Surgical Research. 103(2). 215-222 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Matsukura, A. Yokoi, H. Egawa, T. Kudo, M. Kawashima, Y. Hirata, H. Tanaka, K. Kagajo, H. Wada, K. Tanaka: "Significance of serial real-time pcr monitoring of ebv genome load in living donor liver transplantation"Clinical Transplantation. 16. 107-112 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Tanaka, T. Kiuchi: "Living-donor liver transplantation in the new decade: perspective from the twentieth to the twenty-first century"Journal of Hepatobiriary Pancreat Surg. 9. 218-222 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Goto, S. Masuda, H. Saito, S. Uemoto, T. Kiuchi, K. Tanaka, K. Inui: "C3435T polymorphism in the Mdrl gene affects the enterocyte expression level of Cyp3a4 rather than Pgp in recipients of living-donor liver transplantation"Parmacogenetics. 12. 451-457 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A. Yokoi, S. Sakamoto, Y. Fujimoto, Y. Inomata, K. Tanaka: "Long-term results of living donor liver transplantation for biliary atresia"The 32nd Annual Meeting of The Pacific Association of Pediatric Surgeons, Beijing, China. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Takatsuki, S. Uemoto, S. Sakamoto, Y. Inomata, K. Tanaka: "Weaning of Immunosuppression in living donor liver transplantation outcome"17th The Transplantation Society of Australia and Ne Zealand, Canberra, Australia. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Egawa, T. Matshkura, A. Yokoi, T. Kudo, K. Tanaka: "Significance of serial quantitative monitoring of EBV genome load by real-time PCR in short term and long term follow-up of EBV related disorder in recipients of living donor liver transplantation"American Society of Transplantation (AST), Chicago, USA. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Iwasaki, S. Uemoto, A. Yokoi, K. Tanaka: "Pediatric living donor liver transplantation: a single center experience for 10 years"International Liver Transplantation Society, Chicago, USA. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A. Yokoi, E. Nishimura, F. Oike, T. Kiuchi, S. Uemoto, K. Tanaka: "Weaning of immunosuppression in living donor liver transplant recipients"International Liver Transplantation Society, Berlin, Germany. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] F. Oike, A. Yokoi, S. Uemoto, H. Egawa, T. Kiuchi, K. Tanaka: "Complete withdrawal of immunosuppression in living donor liver transplantation"Meeting of the European Society for Organ Transplantation, Lisboa, Porugal. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] F. Oike: "Complete withdrawal of immunosuppression in living-donor liver transplantation"Abdominal Organ transplantation from living donors: state of the art, Second International congress on immunosuppreion Italy (Gubbio). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Ogura, F. Dike, T. Kiuchi, H. Egawa, S. Kaihara, M. Kasahara, K. Tanaka: "Complete withdrawal of immunosuppression in living donor liver transplantation"American Transplant Congress, USA. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Kiuchi, S.Uemoto, H.Egawa, S.Kaihara, F.Oike, A.Yokoi, Y.Ogura, M.Kasahara, Y.Fujimoto, K.Tanaka: "Living Donor liver Transplantation In Kyoto, 2001 (Chapter 18)"Clinical Transplats 2001. 195-201 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M Shimamura: "Roles Of The Jejunum And Ileum In The First-pass Effect As Absorptive Barriers For Orally Administered Tacrolimus"Journal Of Surgical Research. 103(2). 215-222 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T Matsukura: "Significance Of Serial Real-Time Pcr Monitoring Of Ebv Genome Load In Living Donor Liver Transplantation"Clinical Transplantation. 16. 107-112 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tetsuya Kiuchi: "Living Donor Liver Transplantation In Kyoto, 2001"Clinical Transplats 2001. Chapter 18. 195-201 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koichi Tanaka: "Living-donor Liver Transplantation In The New Decade : Perspective From The Twentieth To The Twenty-First Century"Journal Of Hepatobiriary Pancreat Surg. 9. 218-222 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Maki Goto: "C3435T Polymorphism In The Mdr1 Gene Affects The Enterocyte Expression Level Of Cyp3a4 Rather Than Pgp In Recipients Of Living-Donor Liver Transplantation"Parmacogenetics. 12. 451-457 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 尾池文隆: "生体肝移植における臨床的免疫寛容"今日の移植. 15(4). 358-361 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 上田幹子, 田中紘一: "肝移植の長期予後"小児科. 43(11). 1652-1656 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 上田幹子, 田中紘一: "小児科学 第2版 肝移植"医学書院. 189-191 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koichi Tanaka, et al.: "Living andcadaveric split-liver donation : method of overcoming a shortage in liver transplantation"Curr Opin Organ Transplant. 6. 56-63 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasuhiro Ogura, et al.: "Apotosis and allograft pejection in the absence of CD8+T cell S1"Transplantation. 71・12. 1872-1834 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yukihiro Inomata, et al.: "Pathogenesis and treatment of bile duct loss after liver transplantation"J Hepatobiliary Pancreat Surg. 8. 316-322 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Fukatsu, et al.: "Population pharmacokinetics of tacrolimus in adultrecipients recieving living-donor liver transplantation"Eur J Clin Pnarmacol. 57. 479-484 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koji Takakura, et al.: "Clinical implications of flow cytomentry crossmatch with T or B cells in living donor liver transplantation"Clinical Transplantation. 15. 309-316 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mitsuhisa Takatsuki et al.: "Weaning of immunosuppression in living donor liver transplantat recipients"Transplantation. 72・3. 449-454 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koichi Tanaka: "Current status of living donor liver transplantation In adults"Current Opinion In Organ Transplantation. 5・2. 74-79 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 上本伸二: "小児生体部分肝移植"臨床外科. 55・1. 55-59 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 猪股裕紀洋: "生体部分肝移植の治療成績"外科治療. 82・2. 171-178 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 田中紘一: "マイクロキメリズムと臓器移植"免疫Immunology Frontier. 10・2. 35-39 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 田中紘一: "小児肝臓ならびに小腸移植"日本医師会雑誌. 124. 686-687 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] MITSUHISA TAKATSUKI: "WEANING OF IMMUNOSUPPRESSION IN LIVING DONOR LIVER TRANSPLANT RECIPIENTS"Transplantation. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Inomata: "Living Donor Liver Transplantation: An 8-Year Experience With 379 Consecutive Cases"Transplantation Proceedings. 31. 381 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Kasahara: "Postoperative flow cytometry crossmatch in Living donor liver transplantation"Transplantation. 67(4). 568-575 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kenichiro Seino: "Soluble forms of CD95 ligand after living rerated liver transplantation"Transplantation. 67(4). 634-636 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sachiko Minamiguchi: "Living related liver transplantation: Histopathologic analysisi of graft dysfunction in 304 patients"Human Pathology. 30(12). 1479-1487 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 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)

    • Related Report
      1999 Annual Research Report
  • [Publications] 高槻光寿: "生体肝移植後の免疫抑制剤減量・離脱の試み"今日の移植. 13(1). 19-23 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 田中紘一: "内科学第7版 肝移植 PP250-252"朝倉書店. 2110 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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