1990 Fiscal Year Final Research Report Summary
Development of Alloreactive T-Cell Depletion for the Prophylaxis of GVHD.
| Project/Area Number |
01570549
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Tokai University School of Medicine |
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Principal Investigator |
KATO Shunichi Tokai University School of Medicine Department of Pediatrics Associate Professor, 医学部, 助教授 (70096212)
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| Co-Investigator(Kenkyū-buntansha) |
YABE Hiromasa same as above, Instructor, 医学部, 助手 (70220217)
YABE Miharu same as above, Assistant Professor, 医学部, 講師 (40172514)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Allogeneic BMT / GVHD / Alloreactive T-cell / Galactose Oxidase |
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| Research Abstract |
In this study we attempted to develop a method which will selectively deplete a particular population of T cells that recognizes surfece alloantigen of recipient cells. Galactose oxidase was labeled onto the surface of mitomycin-C (MMC) treated splenic lymphocytes from BALB/C mice (H-2^d, Mls^b). Mouse splenic lymphocytes from DBA/2 (H-2^d, Mls^a) mixed with the galactose oxidase labelled BALB/C lymphocytes allowed to DBA/2 cells which recognized the Mls^b on the BALB/C cells to make direct contact with the galactose oxidase labeled BALB/C cells. By adding galactose, sodium iodide and catalase to the mixture, the contacting stimulator cells which generate hydrogen peroxide in the vicinity of the contacting responder cells and the iodine ions will exert a toxic effect on the responder cells while non-specific toxicity was prevented by catalase. When fresh MMC-treated BALB/C lymphocytes were added to the cell mixture, the mixed lymphocyte cell reaction against BALB/C cells by the treated DBA/2 lymphocytes was abolished. On the other hand, when fresh MMC-treated lymphocytes from C57BL/6 mice (H-2^b, Mls^b) were mixed with the treated DBA/2 cells, the mixed lymphocyte response against C57BL/6 cells by the treated DBA/2 lymphocytes was partially retained. Therefore, although some non-specific toxicity was present, a method to deplete specific T-lymphocyte which recognize major histcompatibility antigen from a mixed cell population while maintaining immune responsiveness towards other antigens was developed. Application of this method to human immune system resulted in failure because of greater stability of human lymphocyte to hydrogen peroxide. This method may have a beneficial effect on the control of post transplant immunity and may be used as a prophylaxis of graft-versus-host disease with some modification.
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