1992 Fiscal Year Final Research Report Summary
Analysis of reiection mechanism of human hematopoietic cell xenotransplantation in immunodeficiency mice
| Project/Area Number |
03680043
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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 |
Laboratory animal science
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| Research Institution | Tokai University |
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Principal Investigator |
SHIMAMURA Kazuo Tokai University School of Medicine, Dept. of Pathol., Assistant professor, 医学部, 講師 (00119679)
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| Co-Investigator(Kenkyū-buntansha) |
TAMAOKI Norikazu Tokai University School of Medicine, Dept. of Pathol., professor, 医学部, 教授 (50055860)
UEYAMA Yoshito Tokai University School of Medicine, Dept. of Pathol., Associate professor, 医学部, 助教授 (30072408)
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| Project Period (FY) |
1991 – 1992
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| Keywords | X-linked immunodeficiency / NK activity / Hematopoietic cells / Xenotransplantation / ADCC |
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| Research Abstract |
In order to elucidate the factors influencing the takes human hematopoietic cells in nude mice, we compared the transplantability of lymphoid neoplasm in nude mice with additional genetic defects in the immune system. The nude mice strains tested were classified as follows by expression of the beige gene and x-linked immunodeficiency (xid) gene : 1) high NK nude (C57BL/6N nu/nu), 2) low NK nude (C57BL/6 bg/bg nu/nu), 3) high NK nude with B cell defect (CBA/N nu/nu), and 4) low NK nude with B cell defect (NIH(S)III). Takes of human xenografts including T cell lymphoma and B cell lymphoma were better in nude mice with xid (CBA/N and NIH(S) III nude mice) then in nude mice without xid (B6 and beige nude mice). In addition, among the nude mice with xid expression, the takes were slightly better in nude mice with a CBA/N background than in those with a NIH(S) background. Moreover, the xenotransplantation rate in (CBA/N x C57BL/6N)F_1 male nude mice with xid expression was higher than in (C57BL/66 x CBA/N)F_1 males without xid expression but did not reach same level as that in CBA/N nude. On the other hand, introduction of the beige gene in nude mice minimally improved the takes of human tumor xenografts under limited experimental conditions ( inoculation of 100x10^5 T cell lymphoma) despite the reduction of NK activity. Although nude mice with human lymphoma xenografts were able to produce antibodies against the human tumors, no or little antibody against the xenografts was observed in CBA/N nude mice sera. In addition, rejection of human lymphoid tumor xenografts was mediated by NK cells using antibody dependent cellular cytotoxicity (ADCC). The results in present report confirmed the effect of xid on human tumor xenografts in nude mice, suggesting the existence of antibodies, possibly present in serum IgM mediating rejection of the hematopoietic cell xenografts by ADCC.
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[Publications] Maruo, K., Shimamura, K., Hioki, K., Itoh, M., Ueyama, Y., Tamaoki, N.: "Role of x-linked immunodeficiency(xid) and NK activity in rejection of human tumors xenotransplanted in nude mice." APMIS. (1993)
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[Publications] Ito, T., Shimamura, K., Shoji, K., Akatsuka, A., Kiryu, Y., Tamaoki, N. Osamura, Y.: "Urinary bladder carcinoma producing granulocyte colony stimulating factor (G-CSF)-A case report with immunohistochemistry-" Virchows Archiv A. (1993)
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「研究成果報告書概要(欧文)」より
