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1996 Fiscal Year Final Research Report Summary

Development of the new monitoring system for acute rejection in clinicallung and lung-heart transplantation, focusing on the cytotoxicity specific to the major histocompatibility complex class I antigens of the donor organ.

Research Project

Project/Area Number 06557070
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section試験
Research Field Thoracic surgery
Research InstitutionUniversity of Tokyo

Principal Investigator

NAKAJIMA Jun  University of Tokyo Hospital, Dept. Cardiothoracic Surgery, Secretary General, 医学部・附属病院, 助手 (90188954)

Co-Investigator(Kenkyū-buntansha) ONO Minoru  University of Tokyo Hospital, Dept. Cardiothoracic Surgery, Staff, 医学部・附属病院, 助手 (40270871)
TAKEDA Makoto  University of Tokyo Hospital, Dept. Cardiothoracic Surgery, Staff, 医学部・附属病院, 助手 (10236482)
KAWAUCHI Motohiro  University of Tokyo Hospital, Dept. Cardiothoracic Surgery, Assistant Professor, 医学部・附属病院, 講師 (00152918)
FURUSE Akira  University of Tokyo Hospital, Dept. Cardiothoracic Surgery, Professor, 医学部・附属病院, 教授 (70010163)
Project Period (FY) 1994 – 1996
Keywordslung transplantation / acute rejection / bronchoalveolar lavage fluid / cytotoxic T cell / major histocompatibility complex / B-lymphoblastoid cell line / interleukin-10 / mixed lymphocyte culture
Research Abstract

This research aimed to establish the monitoring system for acute rejection in cliniacal lung and heart-lung transplantation (LTX and HLTX). For this purpose, cytotoxicity of the lymphocytes derived from the recipients were examined. Lymphocytes were isolated from bronchoalveolar lavage (BAL) and used as effector cells in standard cell-mediated lymphocytolysis (CML) assays using a series of B-lymphoblastoid cell lines (LCL) as targets. Mean percent lysis (i. e. Cytotoxicity) of LCL targets was significantly higher during acute rejection without cytomegaloviral (CMV) infection compared to no rejection or CMV infection when these targets shared one or more of the HLA class I sensitizing donor alloantigens ("class I-relevant targets"). Especially it is significantly higher in the early phase of acute rejection classified as "A1" by the pathological working formulation. There was no significant difference in mean percent lysis of LCL targets during CMV infection without rejection. This study provides a functional in vitro assay to further support the clinical and histological diagnosis of acute rejection in the LTX and HLTX patients.
The properties of lung parenchymal cells were then examined to investigate the mechanisms of acute rejection in LTX.In vitro mixed culture of an immortal human airway epithelial cell line and allogeneic lymphocytes was made up to simulate the LTX.In mixed lymphocyte-airway epithelial cell line (ML-AECL), cytotoxic lymphocytes (CTL) were not elicited. We found that interleukin (IL)-10 was secreted from the lymphocytes with the stimulation of the AECL.CTL activity was generated when the ML-AECL was cultured with IL-2. This CTL showed the MHC-class I-specific cytotoxicity against the AECL.It is therefore suggested that lung parenchymal cells were candidates for antigen-presenting cells in the circumstance of inflammatory cytokines.

  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] 大岩 博、中島 淳,他: "FK506の血中及び臓器別濃度 -ニホンザル肺移植における検討-" 移植. 29. 129-134 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉竹 毅、中島 淳,他: "同種肺移植日本猿の移植肺および脾臓におけるTおよびBリンパ球の分布" 日本呼吸器外科学会雑誌. 8. 129-134 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉竹 毅、中島 淳,他: "日本猿における一側同種肺移植後慢性移行期の移植肺および脾臓における主要組適合性抗原(MHC)発現の検討" 日本呼吸器外科学会雑誌. 8. 548-554 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawauchi M,Nakajima J,et al.: "Cardiac xenotransplantation from pig to Japanese monkey with splenectomy,tacrolims,filtration plasmapheresis,and nafamstat mesilate." Transpl.antation Proceedings. 26(3). 1076-1077 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawauchi M,Nakajima J,et al.: "Contribution of T cells in concordant xenoheartrejection." Transpl.antation Proceedings. 26(3). 1193-1194 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawauchi M,Nakajima J,et al.: "Which is the target vessel of lung rejection?A primate heart-lung transplantation study" Transpl.antation Proceedings. 26(4). 2338-2339 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima J,Kawauchi M,et al.: "Characteristic findings of pulmonary arteriography in xenografted lung of the primates" Transplantation Proceedings. 27(1). 310-312 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima J,Ono M,et al.: "Human allogeneic airway epithelial cell line induced lymphocyte to secrete interleukin-10" Transplantation Proceedings. 28(3). 1861-1862 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeda M,Nakajima J,et al.: "Pretreatment with splenectomy and FK506 in xeno-lung transplantation." Transplantation Proceedings. 28(3). 1435-1436 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeda M,Nakajima J,et al..: "Methotrexatein rescuetherapy for xenotransplanted lungs in primates." Transplantation Proceedings. 28(2). 792-793 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawauchi M,Nakajima J,et al.: "Antigenicity of heart valves and vessels : A primate heart transplant study." Transplantation Proceedings. 28(3). 1824-1825 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawauchi M,Nakajima J,et al.: "Which are the target vessels of xeno-and allo-lung rejection?A primate single lung transplanttion study." Transplantation Proceedings. 28(3). 1416-1417 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima J,Ono M,et al.: "The role of costimulatory molecules on an airway epithelial cells acting as an alloantigenpresenting cells." Transplantation Proceedings. in press. (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] "Problems in xenografted lung of the primates. In : Update Clinical Immunology,Molecular Science in Organ Transplantation." Pabst Science Publishers,Langerich,Germany (in press), (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oiwa H,Nakajima J,Kawauchi M,Takeda M,Furuse A: "The distribution of FK506 in the blood and other organs on a non-human primate model of lung transplantation." Japanese Journal of Transplantation. 29 (4). 144-148 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshitake T,Sugawara I,Furuse A,Kawauchi M,Nakajima J,Takeda M: "Expression of major histocompatibility complex (MHC) antigens after single lung allo-transplantation of Japanese monkey." The Journal of the Japanese Association for Chest Surgery. 8 (5). 548-554 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshitake T,Sugawara I,Nakajima J,Kawauchi M,Furuse A: "T and B cell populations in transplanted lung and spleen of single lung allo-transplanted Japanese monkey." The Journal of the Japanese Association for Chest Surgery. 8 (2). 129-134 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawauchi M.Takeda M.Nakajima J.Matsumoto J.Furuse A.: "Cardiac xenotransplantation from pig to Japanese monkey with splenectomy, tacrolims, filtration plasmapheresis, and nafamstat mesilate." Transplantation Proceedings. 26 (3). 1076-7 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawauchi M.Takeda M.Nakajima J.Matsumoto J.Furuse A.: "Contribution of T cells in concordant xenoheart rejection." Transplantation proceedings. 26 (3). 1193-4 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawauchi M.Matsumoto J.Takeda M.Nakajima J.Furuse A.Oka T.Yoshitake T.: "Which is the target vessel of lung rejection? A primate heart-lung transplantation study." Transplantation Proceedings.26 (4). 2338-9 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima J,Kawauchi M,Kawaguchi G,Takeda M,Matsumoto J,Furuse A: "Characteristic findings of pulmonary arteriography in xenograftedlung of the primates" Transplantation Proceedings. 27 (1). 310-312 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima J,Ono M,Kobayashi J,Kawauchi M,Takeda M,Furuse A: "Human allogeneic airway epithelial cell line inducedlymphocyte to secrete interleukin-10" Transplantation Proceedings. 28 (3). 1861-1862 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeda M,Kawauchi M,Nakajima J,Furuse A: "Pretreatment with splenectomy and FK506 in xeno-lung transplantation" Transplantation Proceedings. 28. 1453-1436 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeda M.Kawauchi M.Nakajima J.Furuse A.: "Methotrexate in rescue therapy for xenotransplanted lungs in primates." Transplantation Proceedings.28 (2). 792-3 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawauchi M,Tanaka K,Nakajima J,Takeda M,Oka T,Furuse A: "Antigenicity of heart valves and vessels : A primate heart transplant study" Transplantation Proceedings. 28. 1824-1825 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawauchi M,Takeda M,Matsumoto J,Nakajima J,Furuse A,Oka T,Yoshitake T: "Which are the target vessels of xeno-and allo-lung rejection? A primate single lung transplantation study." Transplantation Proceedings. 28. 1416-1417 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima J,One M,Takeda M,Kawauchi M,Furuse A,Takizawa H: "The role of costimulatory molecules on a airway epithelial cells acting as an alloantigen-presenting cells.19GC13 : Transplantation Proceedings" (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jun Nakajima :: Problems in xenogrofted lung of the primates.Update Clinical Immunology, Molecular Science in Organ Transplantation, edited by D.Troitzsch, et al. : Pabst Science Publishers, Langerich, Germany (1997, in press), (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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