1991 Fiscal Year Final Research Report Summary
Studies on the Mechanism of Induction of Autoimmune Disease by the Novel Lymphoproliferation gene, lpr^<cg>
| Project/Area Number |
02454167
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Institute of Medical Science, University of Tokyo |
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Principal Investigator |
MATSUZAWA Akio Institute of Medical Science, University of Tokyo, Associate Professor, 医科学研究所, 助教授 (50012745)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Hidetoshi Aichi Cancer Center Research Insitute, Section Chief, 研究所, 室長 (60101119)
KATAGIRI Takuya Institute of Medical Science, University of Tokyo, Assistant Researcher, 医科学研究所, 助手 (70126100)
KIMURA Mikio Institute of Medical Science, University of Tokyo, Assistant Researcher, 医科学研究所, 助手 (90114462)
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| Project Period (FY) |
1990 – 1991
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| Keywords | Mouse / Autoimmune disease / lpr^<cg> gene / Lymphadenopathy / Double-negative T cells / gld gene / Thymus / Autoantibody |
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| Research Abstract |
Several mice with generalized lymphadenopathy were found in the CBA/KlJms (CBA) colony maintained at the Laboratory Animal Research Center. A new mutant strain of mice that develop massive lymphoid hyperplasia at 100% incidence within 5 months of age was established by crossing these diseased mice. Genetic analyses revealed that lymphadenopathy is controlled by a single autosomal recessive gene which is allelic with lpr but can complement qld on chromosome 1 in the induction of swelling of lymph nodes (LN). Thus, the new mutant gene was named lpr^<cg> and the mutant strain was designa Led CBA-lpr^<cg>/lpr^<cg> (CBA-lpr^<cg>). Mutant mice developed hypergammaglobulinemia and various autoantibodies, and their swelled LN were composed of Thy-l^+CD4^-CD8^-B220^+ lymphoid cells or "double-negatice (DN)" T cells. Bone marrow (BM) transfer from CBA-lpr^<cg> to CBA-+/+ (CBA-+) mice caused autoantibody formation but not lymphadenopathy. We developed a simple technique for whole LN transplantati
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on to, demonstrate that lpr^<cg> DN T cells could home into lpr^<cg> and lpr LN but not into gld and + LN. Therefore, the lpr and gld genes are different from each other in the phenotype expression at the LN site. LN from mice heterozygous for both lpr^<cg> and gld (1pr^<cg>-gld mice) allowed homing of 1pr^<cg> DN T cells in support of the cooperativity between lpr^<cg> and gld. Despite milder lymphadenopathy in lpr^<cg>-gld mice, the expanding LN cells showed the same pattern of surface markers as that in lpr^<cg> and gld mice. Serum immunoglobulin and autoantibody levels of IgM class but not those of IgG class were elevated in lpr^<cg> and gld mice. Serum IgG from ILRO and lpr^<cg>-gld mice induced interleukin 3 in an interleukin 3-dependent cell line in relation to the severity. of lymphadenopathy. Athymic lpr^<cg> mice were constructed to investigate the role of the thymus in induction of lymphadenopathy by lpr^<cg>. LN swelling occurred with thymus grafts regardless of their genetic backgrounds but not without them, indicating that the thymus is essential for abnormal differentiation of BM cells into DN T cells. The lpr^<cg> gene is being mapped on chromosome 19. Less
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[Publications] Matsuzawa,A.,Moriyama,T.Kaneko,T.,Tanaka,M.,Kimura,M.,Ikeda,H.,and Katagiri,I.: "A new allele of the lpr locus,lpr^<cg>,that complements the gld genein induction of lymphadenopathy in mouse" Journal Experimental Medicine. 171. 519-531 (1990)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kimura,M.,Mohri,H.,Shimada,K.,Matsuzawa,A.,Wakabayashi,T.and Kanai,Y.: "Serological and histological characterization of the new mutant strain of lpr mice,CBA/KlJms-lpr^<cg>/pr^<cg>" Clinical and Experimental Immunology. 79. 123-129 (1990)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kimura,M.,Katagiri,T.,Kikuchi,Y.,Shimada,K.,Wakabayashi,T.and Matsuzawa,A.: "Role of bone marrow cells in autoantibody production and lymphoproliferation in the novel mutant strain of mice,CBA/KlJms-lpr^<cg>/lpr^<cg>" European Journal of Immunology. 21. 63-69 (1991)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kimura,M.,Ogata,Y.,Shimada,K.,Moriyama,T.and Matsuzawa,A.: "New Mutant mice of autoimmunity,CBA/KlJms-lpr^<cg>/lpr^<cg>,that could link the lpr and gld genes" Autoimmunity. 9. 359-361 (1991)
Description
「研究成果報告書概要(和文)」より
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[Publications] Sato,E.,Iwamoto,M.,Sakihama,T.,Yokoyama,Y.Hamada,Y.,Matsuzawa,A.: "Serum lgG from CBA/KlJms-lpr^<cg>/lpr^<cg> mice induces interleukin-3 in an interleukin-3-dependent cell line-possible correlation with lymphadenopathy" Cellular Immunology. 138. 372-380 (1991)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kimura,M.,Ogata,Y.,Shimada,K.,Wakabayashi,T.Onoda,H.,Katagiri,T.and Matsuzawa,A.: "Nephritogenicity of the lpr^<cg> gene on the MRL background" Immunology. (1992)
Description
「研究成果報告書概要(和文)」より
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[Publications] Matsuzawa, A., Moriyama, T., Kaneko, T., Tanaka, M., Kimura, M., Ikedq, H. and Katagiri, T.: "A new allele of the lpr locus, lpr^<cg>, that complements the gld gene in induction of lymphadenopathy in the mouse" J. Exp. Med.171. 519-531 (1990)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kimura, M., Mohri, H., Shimada, K., Matsuzawa, A., Wakabayashi, T., and Kanai, Y.: "Serological and histological characterization of the new mutant strain of lpr mice, CBA/KlJms-lpr^<cg>/lpr^<cg>" Clin. Exp. Immunol.79. 123-129 (1990)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kimura, M., Katagiri, T., Kikuchi, Y., Shimada, K., Wakabayashi, T. and Matuzawa, A.: "Role of bone marrow cells in autoantibody production and lymphoproliferation in the novel mutant strain of mine, CBA/KlJms-lpr^<cg>/lpr^<cg>." Eur. J. Immunol.21. 63-69 (1991)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kimura, M., Ogata, Y., Shimada, K., Moriyama, T. and Matsuzawa, A. :"New mutant mice of autoimmunity, CBA/KlJms-lpr^<cg>/lpr^<cg>, that could link the lpr and gld genes." Autoimmunity. 9. 359-361 (1991)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sato. E., Iwamoto, M., Sakihama, T., Yokoyama, Y., Hamada, Y., Matsuzawa, A., Akamatsu, n., Nakajima, Y. and Tasaka, k.: "Serum IgG from CBA/KlJms-lpr^<cg>/lpr^<cg> mice induces interleukin-3 in an interleukin-3-dependent cell line-possible correlation with lympadenopathy." Cell. Immunol.138. 372-380 (1991)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kumura, M., Ogata, Y., Shimada, K., Wakabayashi, T., Onoda, H., Katagiri, T. and Matsuzawa, A.: "Nephritogenicity of the lpr^<cg> gene on the MRL background." Immunology. (1992)
Description
「研究成果報告書概要(欧文)」より
