2002 Fiscal Year Final Research Report Summary
Genetic control of the spontaneous activation of CD4+ Th cells in systemic lupus erythematosus (SLE)-prone (NZB x NZW) F1 mice
| Project/Area Number |
12670444
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | Toin University of Yokohama |
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Principal Investigator |
NISHIMURA Hiroyuki Professor, Toin Human Science and Technology Center, Toin University of Yokohama, 工学部, 教授 (60189313)
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| Co-Investigator(Kenkyū-buntansha) |
KODERA Yo Associate Professor, Toin University of Yokohama and Technology Center, Toin University of Yokohama, 工学部, 助教授 (80205426)
OZAKI Shoichi Associate Professor, Department of Medicine and Clinical Science, Kyoto University School of Medicine, 医学部, 講師 (00231233)
ISHIKAWA Sho Lecturer, Department of Pathology, Juntendo University School of Medicine, 医学部, 講師 (00276479)
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| Project Period (FY) |
2000 – 2002
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| Keywords | systemic autoimmune diseases / SLE / New Zealand mice / (NZB x NZW) F1 / NZB mice / NZW mice / CD4+Th cells / CD69 |
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| Research Abstract |
The F1 hybrid of NZB (New Zealand Black) and NZW (New Zealand White) strains of mice has been studied as a murine model of systemic lupus erythematosus (SLE). In the hybrid mice, B1 (CD5+) cells were shown to be responsible for the autoantibody production. However, expression of SLE phenotypes of these mice is strictly dependent on CD4+ T cells. These mice show an age-dependent spontaneous activation and subset skewing of peripheral CD4+ T cells as reflected by the abnormal cytokine productions, elevated frequency of CD4+ T cells positive for an early activation marker CD69, and decreased frequencies of CD4+ T cells positive for the differentiation markers CD62L and/or NTA260. To study the genetic control of abnormal features of peripheral CD4^+ T cells in the ( NZB x NZW) F1 mice, we conducted genome-wide mapping of the quantitative trait loci (QTL) regulating the frequencies of CD69+CD4+, CD62L+CD4+ and NTA260+CD4+ T cells in the spleens of (NZB x .NZW) F1 x NZW backcross mice. Elevated frequency of CD69+CD4+ T cells, and decreased frequencies of CD62L+CD4+ and NTA260+CD4+ T cells were under the common multigenic control, in which interaction of the heterozygosity of the MHC class II loci and a hitherto unknown locus designated as Sta-1 ( spontaneous T-cell activation ) on chromosome 12 plays a major role. These genetic interactions were distinct from those involved in the abnormal functions of B1 cells. Therefore, in (NZB x NZW) F1 mice, abnormal functions of CD4+ T cells and B1 cells are based on distinct multi-genetic predisposition, both of which contribute to the manifestation of SLE phenotypes of the hybrid mice.
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[Publications] Saito T, Kumagai Y, Hiramatsu T, Kurosawa M, Sato S, Habu S, Mitsui K, Kodera Y, Hiroto M, Matsushima A, Inada Y, Nishimura H: "Immune tolerance induced by polyethylene glycol-conjugate of protein antigen : clonal deletion of antigen-specific Th cells in the thymus"J.Biomater. Sci. Polymer Edn.. 11. 647-656 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ochiai K, Ozaki S, Tanino A, Watanabe S, Ueno T, Mitsui K, Toei J, Inada Y, Hirose S, Shirai T, Nishimura H: "Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-probe New Zealand Black mice"Int. Immunol.. 12. 1-8 (2000)
Description
「研究成果報告書概要(欧文)」より
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