| Project/Area Number |
05557032
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | TOKYO UNIVERSITY |
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Principal Investigator |
ASANO Yoshihiro UNIVERSIT OF TOKYO,FACULTY OF MEDICINE,DEPARTMENT OF IMMUNOLOGY,ASSOCIATE PROFESSOR, 医学部, 助教授 (70114353)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Tadahiro SUMITOMO PHARMACEUTICAL CO.RESEARCH INSTITUTE RESEARCHER, 研究所, 研究員
井上 忠広 住友製薬(株), 住友製薬研究所, 研究員
久保 秀一 東京大学, 医学部(医), 助手 (00251223)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1994: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | GVHD / CELL DEATH / CLASS I / TH CELL CLONE / MONOCLONAL ANTIBODY / 骨髄移植 / 移植片対宿主反応 / 活性化リンパ球 |
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| Research Abstract |
The present study was carried out to develop a specific method to inhibit the graft versus host disease which may occur in organ transplantation and blood transfucion. For this purpose, we used a monoclonal antibody (RE2 antibody) which induces cell death specifically in activated lymphocytes but not resting lymphocytes nor somatic cells.
The features of the RE2 mAb are following : 1) RE2 directly killed IL2-dependent T cell clones, ConA- or LPS-activated spleen cells and lymph node cells, but not thymocyte, without participation of serum complement. Fab fragments of RE2 had no cytolytic activity, while the cross-linking of Fab fragments reconstituted the cytotoxicity. 2) Giant holes on the cell membrane were formed within 5 minutes after the treatment with RE2, as observed by scanning electron microscopy. There was no indication of DNA fragmentation nor swelling of mitochondria during the cytolysis, suggesting that the cell death is neither apoptosis nor typical necrosis. 3) Expression cloning study revealed that RE2 reacts with a family of MHC class I molecules including H-2K^K.
These results provide evidence for a novel pathway of cell death of activated lymphocytes by membrane excitation. It was also speculated that RE2 induces cell death through unknown molecule which associated with MHC class I molecules.
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