1997 Fiscal Year Final Research Report Summary
Amelioration of lpr^<cg>-induced autoimmune diseases with Vbeta8.2-specific viral superantigen and its application to gene therapy in mice
| Project/Area Number |
08457069
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MATSUZAWA Akio University of Tokyo, Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (50012745)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMOTO Takayuki University of Tokyo, Institute of Medical Science, Research Associate, 医科学研究所, 助手 (80202406)
KIMURA Mikio University of Tokyo, Institute of Medical Science, Research Associate, 医科学研究所, 助手 (90114462)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Autoimmune disease / Superantigen / lpr^<cg> gene / Mammary tumor virus / Vbeta8.2+ T cells / MRL mice / Lymphoproliferation / Gene therapy |
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| Research Abstract |
MRL-lpr^<cg>/lpr^<cg> (MRL-lpr^<cg>) mice were established by introducing lpr^<cg> gene into MRL mice by 12 generations of backcross. Their newborns were forster-nursed on FM mothers to establish MRL-lpr^<cg>fFM carrying mouse mammary tumor virus (MMTV) encoding Vbeta8.2-specific superantigen (SAg). One-year survey revealed that MRL-lpr^<cg>fFM mice survived longer and had lower levels of proteinuria than MRL-lpr^<cg>. Autopsy at 3 and 5 months of age demonstrated less severe lymphoproliferative disease in MRL-lpr^<cg>fFM.Histological and immunofluorescent examinations indicated that the incidence of clinical glomerulonephritis was clearly lower and the amount of adhered immune complex was smaller in MRL-lpr^<cg>fFM than in MRL-lpr^<cg> mice. Serological analyzes revealed that the total IgG level and anti-DNA antibody levels of IgG class and IgG2a and IgG3 subclasses were lower in MRL-lpr^<cg>fFM mice. Vbeta8.2+ cells were almost completely depleted in CD4+, CD8+ and CD4-8- T cell populations in MRL-lpr^<cg>fFM mice. These results evidenced that MMTV (FM) SAg ameliorated autoimmune diseases by suppressing autoantibody production through deletion of Vbeta8.2+ cells and support the application of viral SAg to gene therapy.
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[Publications] Suzuki, A., Enari, M., Eguchi, Y., Matsuzawa, a., Nagata, S., Tsujimoto, Y.and Iguchi, T.: "Involvement of Fas in regression of vAginal epithelia after ovariectomy and during an estrous cycle." EMBO.J.15. 211-215 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Miez, A., Itoh, T., Cui, J.Q., Makino, Y., Kawano, T., Tsuchida, K., Koike, T., Shirai, T., Yagita, H., Matsuzawa, A., Koseki, H.and Taniguchi, M.: "Selective reduction of Val4+ NK cells associated with disease development in autoimmune-ptone mice." J.Immunol.156. 4035-4040 (1996)
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[Publications] Kojima, H., Fukuzawa, Y., Sato, T., Enari, M., Tomooka, Y., Matsuzawa, A., Ohta, Y.and Iguchi, T.: "Involvement of the TNF-a system and the Fas system in the induction of apoptosis of mouse mammary gland after weaning." Apoptosis. 1. 201-208 (1996)
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[Publications] Nakano, H., Tamura, T., Yoshimoto, T., Yagita, H., Miyasaka, M., Butcher, E., Nariuchi, H.and Matsuzawa.A.: "Genetic defect in T lymphocyte homing into peripheral lymph nodes." Eur.J.Immunol.27. 215-221 (1997)
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[Publications] Nakano, H., Mori, S., Yonekawa, H., Nariuchi, H., Matsuzawa, A.and Kakiuchi, T.: "A novel mutant gene involved in lymphocyte-specific homing into peripheral lymphoid organs on mouse chromosome 4" Blood. (In press.).
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「研究成果報告書概要(欧文)」より
