| Project/Area Number |
06557070
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
Thoracic surgery
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| Research Institution | University of Tokyo |
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Principal Investigator |
NAKAJIMA Jun University of Tokyo Hospital, Dept. Cardiothoracic Surgery, Secretary General, 医学部・附属病院, 助手 (90188954)
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| 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)
大塚 俊哉 東京大学, 医学部(病), 助手 (80262004)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Keywords | lung transplantation / acute rejection / bronchoalveolar lavage fluid / cytotoxic T cell / major histocompatibility complex / B-lymphoblastoid cell line / interleukin-10 / mixed lymphocyte culture / 凍結保存 / 気道上皮細胞 / BEAS-2B / flow cytometry / programmed freezer / interferon-gamma / HLA-DR / 気道上皮細胞株 / 内皮細胞株 / MHCクラスI、II / フローサイトメトリー / MTT Assay / リンパ球混合培養 / プログラムフリーザ- / Inter fevon-γ / 同種気道上皮細胞株 / リンパ球混合培養糸 / IL-2 / IL-10 / 上清中濃度 / EASIA法 |
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| 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.
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