1995 Fiscal Year Final Research Report Summary
DEVELOPMENT OF MATERIALS WHICH HAVE INHIBITORY ACTIVITY ON GRAFT-VERSUS-HOST DISEASE ACCOPANIED BY BONE MARROW TRANSPLANTATION
| 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
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| Project Period (FY) |
1993 – 1995
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| Keywords | GVHD / CELL DEATH / CLASS I / TH CELL CLONE / MONOCLONAL ANTIBODY |
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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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[Publications] Kubo, S., T.Nakayama, M.Furutani-Seiki, H.Kishimoto, K.Hashimoto, M -J.Bae, T.Yokochi, N.Takeda, S.Aizawa, Y.Asano, and T.Tada: "A novel form of self tolerance in transgenic mice with autoreactive T cell receptor alpha and beta chein genes." Int.Immunol. 6. 593-602 (1994)
Description
「研究成果報告書概要(欧文)」より
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